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  • 1.
    Bergman, Frida
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mattson-Frost, Tove
    Jonasson, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sörlin, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Levine, James
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Installing treadmill workstations in offices does little for cognitive performance and brain structure, despite a baseline association between sitting time and hippocampus volumeManuskript (preprint) (Annet vitenskapelig)
  • 2.
    Blomquist, Caroline
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Alvehus, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Burén, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Larsson, Christel
    Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden..
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderström, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity2017Inngår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 25, nr 5, s. 892-900Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Abdominal fat accumulation after menopause is associated with low-grade inflammation and increased risk of metabolic disorders. Effective long-term lifestyle treatment is therefore needed.

    METHODS: Seventy healthy postmenopausal women (age 60 ± 5.6 years) with BMI 32.5 ± 5.5 were randomized to a Paleolithic-type diet (PD) or a prudent control diet (CD) for 24 months. Blood samples and fat biopsies were collected at baseline, 6 months, and 24 months to analyze inflammation-related parameters.

    RESULTS: Android fat decreased significantly more in the PD group (P = 0.009) during the first 6 months with weight maintenance at 24 months in both groups. Long-term significant effects (P < 0.001) on adipose gene expression were found for toll-like receptor 4 (decreased at 24 months) and macrophage migration inhibitory factor (increased at 24 months) in both groups. Serum interleukin 6 (IL-6) and tumor necrosis factor α levels were decreased at 24 months in both groups (P < 0.001) with a significant diet-by-time interaction for serum IL-6 (P = 0.022). High-sensitivity C-reactive protein was decreased in the PD group at 24 months (P = 0.001).

    CONCLUSIONS: A reduction of abdominal obesity in postmenopausal women is linked to specific changes in inflammation-related adipose gene expression.

  • 3.
    Blomquist, Caroline
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Larsson, Christel
    University of Gothenburg.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Risérus, Ulf
    Uppsala University.
    Long-term effects of a Paleolithic diet on plasma fatty acid composition in postmenopausal women with obesity: a randomized trialManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background: A Paleolithic-type diet (PD) can improve cardiometabolic risk factors, but its impact on plasma fatty acid (FA) composition is unknown. We hypothesized that a PD improves dietary fat quality and FA metabolism, which may help counteract obesity-related metabolic dysfunction. 

    Objective: The current study investigated the impact of a PD on biomarkers of dietary fat quality and indices of FA desaturation and de novo lipogenesis compared with a prudent control diet (CD).

    Design: This randomized 2-year trial included 70 women (mean ± SD age 60 ± 5.6 years, BMI 33 ± 3.4). The PD was rich in fish and vegetable fats but devoid of dairy products and lower in carbohydrates than the CD advised to follow the Nordic Nutrition recommendations. FA composition of plasma cholesterol esters (CE) was assessed using gas chromatography, desaturase activities estimated by product-to-precursor FA ratios, and dietary intake measured by 4-day food records at baseline and after 6 and 24 months.

    Results: Saturated fat (P=0.009) and carbohydrate (P<0.001) intake was lower, whereas polyunsaturated (PUFA), monounsaturated FA, and protein intake were higher at 24 after PD versus CD (all P<0.001). Changes in plasma FA composition during PD compared to CD suggested that saturated FAs from dairy foods were partly replaced with PUFAs from fish and vegetable sources. Although comparable BMI, energy intake, and physical activity were found at 24 months with both diets, metabolic markers and desaturase activity indices, including 16:0 (P=0.005), 16:1n-7 (P=0.002), 20:3n-6 (P=0.004), stearoyl-CoA desaturase 1 (SCD-1) (P=0.006), lipogenic index (P<0.001), and the triglyceride/high-density lipoprotein cholesterol ratio (P=0.031), were lower after 24 months of PD versus CD.

    Conclusions: The PD had long-term effects on dietary fat quality intake and plasma FA composition, changes previously linked to improved cardiometabolic health. The results may suggest an anti-lipogenic effect of PD, possibly contributing to improved dyslipidemia.

  • 4.
    Blomquist, Caroline
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Worrsjö, Evelina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Makoveichuk, Elena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Larsson, Christel
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet2018Inngår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 57, nr 8, s. 2877-2886Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: We studied effects of diet-induced postmenopausal weight loss on gene expression and activity of proteins involved in lipogenesis and lipolysis in adipose tissue.

    Methods: Fifty-eight postmenopausal women with overweight (BMI 32.5 ± 5.5) were randomized to eat an ad libitum Paleolithic-type diet (PD) aiming for a high intake of protein and unsaturated fatty acids or a prudent control diet (CD) for 24 months. Anthropometry, plasma adipokines, gene expression of proteins involved in fat metabolism in subcutaneous adipose tissue (SAT) and lipoprotein lipase (LPL) activity and mass in SAT were measured at baseline and after 6 months. LPL mass and activity were also measured after 24 months.

    Results: The PD led to improved insulin sensitivity (P < 0.01) and decreased circulating triglycerides (P < 0.001), lipogenesis-related factors, including LPL mRNA (P < 0.05), mass (P < 0.01), and activity (P < 0.001); as well as gene expressions of CD36 (P < 0.05), fatty acid synthase, FAS (P < 0.001) and diglyceride acyltransferase 2, DGAT2 (P < 0.001). The LPL activity (P < 0.05) and gene expression of DGAT2 (P < 0.05) and FAS (P < 0.05) were significantly lowered in the PD group versus the CD group at 6 months and the LPL activity (P < 0.05) remained significantly lowered in the PD group compared to the CD group at 24 months.

    Conclusions: Compared to the CD, the PD led to a more pronounced reduction of lipogenesis-promoting factors in SAT among postmenopausal women with overweight. This could have mediated the favorable metabolic effects of the PD on triglyceride levels and insulin sensitivity.

  • 5.
    Chorell, Elin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Mapping the consequenses of physical exercise and nutrition on human health: A predictive metabolomics approach2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Human health is a complex and wide-ranging subject far beyond nutrition and physical exercise. Still, these factors have a huge impact on global health by their ability to prevent diseases and thus promote health. Thus, to identify health risks and benefits, it is necessary to reveal the underlying mechanisms of nutrition and exercise, which in many cases follows a complex chain of events. As a consequence, current health research is generating massive amounts of data from anthropometric parameters, genes, proteins, small molecules (metabolites) et cetera, with the intent to understand these mechanisms. For the study of health responses, especially related to physical exercise and nutrition, alterations in small molecules (metabolites) are in most cases immediate and located close to the phenotypic level and could therefore provide early signs of metabolic imbalances. Since there are roughly as many different responses to exercise and nutrients as there are humans, this quest is highly multifaceted and will benefit from an interpretation of treatment effects on a general as well as on an individual level. This thesis involves the application of chemometric methods to the study of global metabolic reactions, i.e. metabolomics, in a strategy coined predictive metabolomics. Via the application of predictive metabolomics an extensive hypothesis-free biological interpretation has been carried out of metabolite patterns in blood, acquired using gas chromatography-mass spectrometry (GC-MS), related to physical exercise, nutrition and diet, all in the context of human health. In addition, the chemometrics methodology have computational benefits concerning the extraction of relevant information from information-rich data as well as for interpreting general treatment effects and individual responses, as exemplified throughout this work. Health concerns all lifestages, thus this thesis presents a strategic framework in combination with comprehensive interpretations of metabolite patterns throughout life. This includes a broad range of human studies revealing metabolic patterns related to the impact of physical exercise, macronutrient modulation and different fitness status in young healthy males, short and long term dietary treatments in overweight post menopausal women as well as metabolic responses related to probiotics treatment and early development in infants. As a result, the studies included in the thesis have revealed metabolic patterns potentially indicative of an anti-catabolic response to macronutrients in the early recovery phase following exercise. Moreover, moderate differences in the metabolome associated with cardiorespiratory fitness level were detected, which could be linked to variation in the inflammatory and antioxidaive defense system. This work also highlighted mechanistic information that could be connected to dietary related weight loss in overweight and obese postmenopausal women in relation to short as well as long term dietary effects based on different macronutrient compositions. Finally, alterations were observed in metabolic profiles in relation to probiotics treatment in the second half of infancy, suggesting possible health benefits of probiotics supplementation at an early age.

     

  • 6.
    Chorell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Karlsson, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    West, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    The impact of feeding Lactobacillus F19 during weaning: a study of the plasma metabolomeManuskript (preprint) (Annet vitenskapelig)
  • 7.
    Chorell, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hall, Ulrika Andersson
    Gustavsson, Carolina
    Berntorp, Kerstin
    Puhkala, Jatta
    Luoto, Riitta
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Holmäng, Agneta
    Pregnancy to postpartum transition of serum metabolites in women with gestational diabetes2017Inngår i: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 72, s. 27-36Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: Gestational diabetes is commonly linked to development of type 2 diabetes mellitus (T2DM). There is a need to characterize metabolic changes associated with gestational diabetes in order to find novel biomarkers for T2DM. Objective: To find potential pathophysiological mechanisms and markers for progression from gestational diabetes mellitus to T2DM by studying the metabolic transition from pregnancy to postpartum. Design: The metabolic transition profile from pregnancy to postpartum was characterized in 56 women by mass spectrometry-based metabolomics; 11 women had gestational diabetes mellitus, 24 had normal glucose tolerance, and 21 were normoglycaemic but at increased risk for gestational diabetes mellitus. Fasting serum samples collected during trimester 3 (gestational week 32 +/- 0.6) and postpartum (10.5 +/- 0.4 months) were compared in diagnosis-specific multivariate models (orthogonal partial least squares analysis). Clinical measurements (e.g., insulin, glucose, lipid levels) were compared and models of insulin sensitivity and resistance were calculated for the same time period. Results: Women with gestational diabetes had significantly increased postpartum levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, and their circulating lipids did not return to normal levels after pregnancy. The increase in BCAAs occurred postpartum since the BCAAs did not differ during pregnancy, as compared to normoglycemic women. Conclusions: Postpartum levels of specific BCAAs, notably valine, are related to gestational diabetes during pregnancy.

  • 8.
    Chorell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Moritz, Thomas
    Branth, Stefan
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    A predictive metabolomics evaluation of nutrition-modulated metabolic stress responses in human blood serum during the early recovery phase of strenuous physical exercise2009Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 8, nr 6, s. 2966-77Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have investigated whether postexercise ingestion of carbohydrates in combination with proteins generates a different systemic metabolic response, as compared to the sole ingestion of carbohydrate or water, in the early recovery phase following exercise. In addition, metabolic patterns related to fitness level were studied together with individual responses to nutritional modulation. Twenty-four male subjects were exposed to 90 min of ergometer-cycling. Each participant was subject to four identical test-sessions, including ingestion of one of four beverages (water, low-carbohydrate beverage, high-carbohydrate beverage, and low-carbohydrate−protein beverage (LCHO-P)) immediately after cycling. Blood was collected at six time points, one pre- and five postexercise. Extracted blood serum was subject to metabolomic characterization by gas chromatography/time-of-flight mass spectrometry (GC−TOF MS). Data was processed using hierarchical multivariate curve resolution (HMCR), and multivariate statistical analysis was carried out using orthogonal partial least-squares (OPLS). Predictive metabolomics, including predictive HMCR and OPLS classification, was applied to ensure efficient sample processing and validation of detected metabolic patterns. Separation of subjects in relation to ingested beverage was detected and interpreted. Pseudouridine was suggested as a novel marker for pro-anabolic effect following LCHO-P ingestion, which was supported by the detected decrease of the catabolic marker 3-methylhistidine. Separation of subjects according to fitness level was achieved, and nutritional modulation by LCHO-P was shown to improve the metabolic status of less fit subjects in the recovery phase. In addition, the potential of the methodology for detection of early signs of insulin resistance was also demonstrated.

  • 9.
    Chorell, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Norrlands University Hospital, Umeå University, Umeå, Sweden .
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Larsson, Christel
    Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden.
    Sandberg, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Plasma metabolomic response to postmenopausal weight loss induced by different diets2016Inngår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 12, nr 5, artikkel-id 85Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Menopause is associated with increased abdominal fat and increased risk of developing diabetes and cardiovascular disease. Objectives The present study evaluated the plasma metabolic response in relation to insulin sensitivity after weight loss via diet intervention. Methods This work includes two studies; i) Ten women on a 5 weeks Paleolithic-type diet (PD, 30 energy percent (E%) protein, 40 E% fat, 30 E% carbohydrates), ii) 55 women on 6 months of either PD or Nordic Nutrition Recommendations diet (NNR, 15 E% protein, 30 E% fat, and 55 E% carbohydrates). Plasma metabolic profiles were acquired at baseline and post diet using gas chromatography time-of-flight/mass spectrometry and investigated in relation to insulin sensitivity using multivariate bioinformatics. Results Both the PD and NNR diet resulted in significant weight loss, reduced waist circumference, improved serum lipid profiles, and improved insulin sensitivity. We detected a baseline metabolic profile that correlated significantly with insulin sensitivity, and of which components increased significantly in the PD group compared to NNR. Specifically, a significant increase in myo-inositol (MI), a second messenger of insulin action, and beta-hydroxybutyric acid (beta-HB)increased while dihomogamma-linoleic acid (DGLA) decreased in PD compared to NNR, which correlated with improved insulin sensitivity. We also detected a significant decrease in tyrosine and tryptophan, potential markers of insulin resistance when elevated in the circulation, with the PD but not the NNR. Conclusions Using metabolomics, we detected changes in the plasma metabolite profiles associated with weight loss in postmenopausal women by different diets. The metabolic profiles following 6 months of PD were linked to beneficial effects on insulin sensitivity compared to NNR.

  • 10.
    Chorell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Rydberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Larsson, Christel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    A metabolomic evaluation of short and long term effects of different macronutrient intake in overweight and obese postmenopausal womenManuskript (preprint) (Annet vitenskapelig)
  • 11.
    Chorell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Moritz, Thomas
    Swedish University of Agricultural Sciences.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Physical fitness level is reflected by alterations in the human plasma metabolome2012Inngår i: Molecular BioSystems, ISSN 1742-206X, Vol. 8, nr 4, s. 1187-1196Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    An excessive energy intake combined with a low level of physical activity induces detrimental processes involved in disease development, e.g. type 2 diabetes and cardiovascular disease. However the underlying mechanisms for regulation of metabolic capacity and fitness status remain unclear. Metabolomics involves global studies of the metabolic reactions in an organism or cell. Thus hypotheses regarding biochemical events can be generated to increase the understanding of disease development and thereby aid in the development of novel treatments or preventions. We present the first standardized intervention study focusing on characterizing the human metabolome in relation to moderate differences in cardiorespiratory fitness. Gas chromatography-time of flight/mass spectrometry (GC-TOF/MS) was used to characterize 460 plasma samples from 27 individuals divided into two groups based on physical fitness level (VO2max). Multi- and univariate between group comparisons based on 197 metabolites were carried out in samples collected at rest prior to any intervention, over time following a nutritional load or a standardized exercise scheme, with and without nutritional load. We detected decreased levels of gamma-tocopherol (GT), a vitamin E isomer, in response to a high fitness level, whereas the opposite was seen for the alpha isomer (AT). In addition, the high fitness level was associated with elevated ω3-PUFA (DHA, 22:6ω3) and a decrease in ω6-PUFA (18:2ω6) as well as in saturated (16:0, 18:0), monounsaturated (18:1) and trans (16:1) fatty acids. We thus hypothesize that high fitness status induces an increased cardiorespiratory inflammatory and antioxidant defense system, more prone to deal with the inflammatory response following exercise and nutrition intake.

  • 12.
    Chorell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Thysell, Elin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Eklund, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Silfver, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Carlsson, Inga-Britt
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Lundgren, Krister
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Moritz, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    A Multivariate Screening Strategy for Investigating Metabolic Effects of Strenuous Physical Exercise in Human Serum2007Inngår i: Journal of Proteome Research, ISSN 1535-3893, Vol. 6, nr 6, s. 2113-2120Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A novel hypothesis-free multivariate screening methodology for the study of human exercise metabolism in blood serum is presented. Serum gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) data was processed using hierarchical multivariate curve resolution (H-MCR), and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to model the systematic variation related to the acute effect of strenuous exercise. Potential metabolic biomarkers were identified using data base comparisons. Extensive validation was carried out including predictive H-MCR, 7-fold full cross-validation, and predictions for the OPLS-DA model, variable permutation for highlighting interesting metabolites, and pairwise t tests for examining the significance of metabolites. The concentration changes of potential biomarkers were verified in the raw GC/TOFMS data. In total, 420 potential metabolites were resolved in the serum samples. On the basis of the relative concentrations of the 420 resolved metabolites, a valid multivariate model for the difference between pre- and post-exercise subjects was obtained. A total of 34 metabolites were highlighted as potential biomarkers, all statistically significant (p < 8.1E-05). As an example, two potential markers were identified as glycerol and asparagine. The concentration changes for these two metabolites were also verified in the raw GC/TOFMS data.The strategy was shown to facilitate interpretation and validation of metabolic interactions in human serum as well as revealing the identity of potential markers for known or novel mechanisms of human exercise physiology. The multivariate way of addressing metabolism studies can help to increase the understanding of the integrative biology behind, as well as unravel new mechanistic explanations in relation to, exercise physiology.

  • 13.
    Chorell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Thysell, Elin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindberg, Johan
    Schuppe-Koistinen, Ina
    Moritz, Thomas
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Statistical multivariate metabolite profiling for aiding biomarker pattern detection and mechanistic interpretations in GC/MS based metabolomics2006Inngår i: Metabolomics, Vol. 2, nr 4, s. 257-68Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A strategy for robust and reliable mechanistic statistical modelling of metabolic responses in relation to drug induced toxicity is presented. The suggested approach addresses two cases commonly occurring within metabonomic toxicology studies, namely; 1) A pre-defined hypothesis about the biological mechanism exists and 2) No such hypothesis exists. GC/MS data from a liver toxicity study consisting of rat urine from control rats and rats exposed to a proprietary AstraZeneca compound were resolved by means of hierarchical multivariate curve resolution (H-MCR) generating 287 resolved chromatographic profiles with corresponding mass spectra. Filtering according to significance in relation to drug exposure rendered in 210 compound profiles, which were subjected to further statistical analysis following correction to account for the control variation over time. These dose related metabolite traces were then used as new observations in the subsequent analyses. For case 1, a multivariate approach, named Target Batch Analysis, based on OPLS regression was applied to correlate all metabolite traces to one or more key metabolites involved in the pre-defined hypothesis. For case 2, principal component analysis (PCA) was combined with hierarchical cluster analysis (HCA) to create a robust and interpretable framework for unbiased mechanistic screening. Both the Target Batch Analysis and the unbiased approach were cross-verified using the other method to ensure that the results did match in terms of detected metabolite traces. This was also the case, implying that this is a working concept for clustering of metabolites in relation to their toxicity induced dynamic profiles regardless if there is a pre-existing hypothesis or not. For each of the methods the detected metabolites were subjected to identification by means of data base comparison as well as verification in the raw data. The proposed strategy should be seen as a general approach for facilitating mechanistic modelling and interpretations in metabolomic studies.

  • 14.
    Chorell, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Videhult, Frida Karlsson
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    West, Christina E
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Impact of probiotic feeding during weaning on the serum lipid profile and plasma metabolome in infants2013Inngår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, nr 1, s. 116-126Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The gut microbiome interacts with the host in the metabolic response to diet, and early microbial aberrancies may be linked to the development of obesity and metabolic disorders later in life. Probiotics have been proposed to affect metabolic programming and blood lipid levels, although studies are lacking in infants. Here, we report on the lipid profile and global metabolic response following daily feeding of probiotics during weaning. A total of 179 healthy, term infants were randomised to daily intake of cereals with (n 89) or without (n 90) the addition of Lactobacillus paracasei ssp. paracasei F19 (LF19) 108 colony-forming units per serving from 4 to 13 months of age. Weight, length and skinfold thickness were monitored. Venous blood was drawn at 5·5 and 13 months of age for analysis of the serum lipid profile. In a subsample, randomly selected from each group, GC-time-of-flight/MS was used to metabolically characterise plasma samples from thirty-seven infants. A combination of multi- and univariate analysis was applied to reveal differences related to LF19 treatment based on 228 putative metabolites, of which ninety-nine were identified or classified. We observed no effects of probiotic feeding on anthropometrics or the serum lipid profile. However, we detected significantly lower levels of palmitoleic acid (16 : 1) (P < 0·05) and significantly higher levels of putrescine (P < 0·01) in LF19-treated infants. Palmitoleic acid is a major MUFA strongly linked to visceral obesity, while putrescine is a polyamine with importance for gut integrity. Whether the observed differences will have long-term health consequences are being followed.

  • 15.
    Chorell, Erik
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Efficient Synthesis of 2-Substituted Phthalimides from Phthalic Acids in One Step2013Inngår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, Vol. 2013, nr 33, s. 7512-7516Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Efficient procedures for synthesizing 2-substituted phthalimide (isoindole-1,3-dione) analogues starting from phthalic acids have been developed by using experimental design. The phthalimide central fragment frequently appears in biologically active compounds, materials, catalysts, and fluorescent probes, and therefore the development of general, fast, and convenient synthetic methods to this scaffold under neutral, acidic, and basic conditions would be attractive. After an initial screening, the use of acetonitrile, acetic acid, or pyridine in combination with microwave heating proved most promising. Experimental design was applied to these conditions to optimize the time, temperature, and concentration. This strategy has successfully generated synthetic methods that have been used to synthesize a series of phthalimides from phthalic acids and various amines or anilines in excellent yields. The developed methods have proven to be general, fast, convenient, and economic, and thus are expected to have broad utility to efficiently construct novel compounds for future biological and chemical applications.

  • 16. Dugas, Lara R.
    et al.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Plange-Rhule, Jacob
    Lambert, Estelle V.
    Cao, Guichan
    Cooper, Richard S.
    Layden, Brian T.
    Scholten, Denise
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Luke, Amy
    Goedecke, Julia H.
    Obesity-related metabolite profiles of black women spanning the epidemiologic transition2016Inngår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 12, nr 3, artikkel-id 45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In developed countries, specific metabolites have been associated with obesity and metabolic diseases, e.g. type 2 diabetes. It is unknown whether a similar profile persists across populations of African-origin, at increased risk for obesity and related diseases. In a cross-sectional study of normal-weight and obese black women (33.3 +/- 6.3 years) from the US (N = 69, 65 % obese), South Africa (SA, N = 97, 49 % obese) and Ghana (N = 82, 33 % obese) serum metabolite profiles were characterized via gas chromatography-time of flight/mass spectrometry. In US and SA women, BMI correlated with branched-chain and aromatic amino acids, as well as dopamine and aminoadipic acid. The relationship between BMI and lipid metabolites differed by site; BMI correlated positively with palmitoleic acid (16: 1) in the US; negatively with stearic acid (18: 0) in SA, and positively with arachidonic acid (20: 4) in Ghana. BMI was also positively associated with sugar-related metabolites in the US; i.e. uric acid, and mannitol, and with glucosamine, glucoronic acid and mannitol in SA. While we identified a common amino acid metabolite profile associated with obesity in black women from the US and SA, we also found site-specific obesity-related metabolites suggesting that the local environment is a key moderator of obesity.

  • 17. Goedecke, J H
    et al.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Livingstone, D E W
    Stimson, R H
    Hayes, P
    Adams, K
    Dave, J A
    Victor, H
    Levitt, N S
    Kahn, S E
    Seckl, J R
    Walker, B R
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women2015Inngår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 39, nr 2, s. 303-311Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Black women have lower visceral adipose tissue (VAT) but are less insulin sensitive than white women; the mechanisms responsible are unknown.

    Objective: The study aimed to test the hypothesis that variation in subcutaneous adipose tissue (SAT) sensitivity to glucocorticoids might underlie these differences.

    Methods: Body fatness (dual energy X-ray absorptiometry) and distribution (computerized tomography), insulin sensitivity (SI, intravenous and oral glucose tolerance tests), and expression of 11β-hydroxysteroid dehydrogenase-1 (11HSD1), hexose-6-phosphate dehydrogenase and glucocorticoid receptor-α (GRα), as well as genes involved in adipogenesis and inflammation were measured in abdominal deep SAT, superficial SAT and gluteal SAT (GLUT) depots of 56 normal-weight or obese black and white premenopausal South African (SA) women. We used a combination of univariate and multivariate statistics to evaluate ethnic-specific patterns in adipose gene expression and related body composition and insulin sensitivity measures.

    Results: Although 11HSD1 activity and mRNA did not differ by ethnicity, GRα mRNA levels were significantly lower in SAT of black compared with white women, particularly in the GLUT depot (0.52±0.21 vs 0.91±0.26 AU, respectively, P<0.01). In black women, lower SAT GRα mRNA levels were associated with increased inflammatory gene transcript levels and abdominal SAT area, and reduced adipogenic gene transcript levels, VAT/SAT ratio and SI. Abdominal SAT 11HSD1 activity associated with increased VAT area and decreased SI in white, but not in black women.

    Conclusions: In black SA women, downregulation of GRα mRNA levels with obesity and reduced insulin sensitivity, possibly via increased SAT inflammation, is associated with reduced VAT accumulation.

  • 18. Goedecke, Julia H.
    et al.
    Mendham, Amy E.
    Clamp, Louise
    Nankam, Pamela A. Nono
    Fortuin-de Smidt, Melony C.
    Phiri, Lindokuhle
    Micklesfield, Lisa K.
    Keswel, Dheshnie
    Woudberg, Nicholas J.
    Lecour, Sandrine
    Alhamud, Ali
    Kaba, Mamadou
    Lutomia, Faith M.
    van Jaarsveld, Paul J.
    de Villiers, Anniza
    Kahn, Steven E.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hauksson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    An Exercise Intervention to Unravel the Mechanisms Underlying Insulin Resistance in a Cohort of Black South African Women: Protocol for a Randomized Controlled Trial and Baseline Characteristics of Participants2018Inngår i: JMIR Research Protocols, ISSN 1929-0748, E-ISSN 1929-0748, Vol. 7, nr 4, artikkel-id e75Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D.

    Objective: The objective of the study was to examine the mechanisms underlying the changes in insulin sensitivity and secretion in response to a 12-week exercise intervention in obese black South African (SA) women.

    Methods: A total of 45 obese (body mass index, BMI: 30-40 kg/m2) black SA women were randomized into a control (n=22) or experimental (exercise; n=23) group. The exercise group completed 12 weeks of supervised combined aerobic and resistance training (40-60 min, 4 days/week), while the control group maintained their typical physical activity patterns, and both groups were requested not to change their dietary patterns. Before and following the 12-week intervention period, insulin sensitivity and secretion (frequently sampled intravenous glucose tolerance test) and its primary and secondary determinants were measured. Dietary intake, sleep quality and quantity, physical activity, and sedentary behaviors were measured every 4 weeks.

    Results: The final sample included 20 exercise and 15 control participants. Baseline sociodemographics, cardiorespiratory fitness, anthropometry, cardiometabolic risk factors, physical activity, and diet did not differ between the groups (P>.05).

    Conclusions: The study describes a research protocol for an exercise intervention to understand the mechanisms underlying insulin sensitivity and secretion in obese black SA women and aims to identify causal pathways underlying the high prevalence of insulin resistance and risk for T2D in black SA women, targeting specific areas for therapeutic intervention.

  • 19.
    Jonsson, Pär
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wuolikainen, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Thysell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Constrained randomization and multivariate effect projections improve information extraction and biomarker pattern discovery in metabolomics studies involving dependent samples2015Inngår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 11, nr 6, s. 1667-1678Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Analytical drift is a major source of bias in mass spectrometry based metabolomics confounding interpretation and biomarker detection. So far, standard protocols for sample and data analysis have not been able to fully resolve this. We present a combined approach for minimizing the influence of analytical drift on multivariate comparisons of matched or dependent samples in mass spectrometry based metabolomics studies. The approach is building on a randomization procedure for sample run order, constrained to independent randomizations between and within dependent sample pairs (e.g. pre/post intervention). This is followed by a novel multivariate statistical analysis strategy allowing paired or dependent analyses of individual effects named OPLS-effect projections (OPLS-EP). We show, using simulated data that OPLS-EP gives improved interpretation over existing methods and that constrained randomization of sample run order in combination with an appropriate dependent statistical test increase the accuracy and sensitivity and decrease the false omission rate in biomarker detection. We verify these findings and prove the strength of the suggested approach in a clinical data set consisting of LC/MS data of blood plasma samples from patients before and after radical prostatectomy. Here OPLS-EP compared to traditional (independent) OPLS-discriminant analysis (OPLS-DA) on constrained randomized data gives a less complex model (3 versus 5 components) as well a higher predictive ability (Q2 = 0.80 versus Q2 = 0.55). We explain this by showing that paired statistical analysis detects 37 unique significant metabolites that were masked for the independent test due to bias, including analytical drift and inter-individual variation.

  • 20.
    Kindahl, Tomas
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Chorell, Erik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Development and optimization of simple one-step methods for the synthesis of 4-amino-substituted 1,8-naphthalimides2014Inngår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, nr 28, s. 6175-6182Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The 1,8-naphthalimide central fragment can be found in a vast number of bioactive compounds and drugs in clinical trials, and can be recognized from their use as fluorescent probes. Of key importance for the fluorescent properties of the scaffold is the 4-amino substituent, which has also proven to be critical in several other chemical and biological applications. Because of the great interest in 1,8-naphthalimides in general, and 4-amino-substituted 1,8-naphthalimides in particular, we have developed and optimized one-step procedures with which to access these derivatives by using an experimental design approach. The multivariate studies of temperature, reaction time, and equivalents of substrates identified conditions with close to quantitative yields that could be applied to generate a range of 4-amino-substituted 1,8-naphthalimides in high yields.

  • 21. Mtintsilana, Asanda
    et al.
    Micklesfield, Lisa K.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Goedecke, Julia H.
    Fat redistribution and accumulation of visceral adipose tissue predicts type 2 diabetes risk in middle-aged black South African women: a 13-year longitudinal study2019Inngår i: Nutrition & Diabetes, ISSN 2044-4052, E-ISSN 2044-4052, Vol. 9, artikkel-id 12Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cross-sectional studies in South Africa (SA) have shown that black SA women, despite being more insulin resistant, have less visceral adipose tissue (VAT) and more subcutaneous adipose tissue (SAT) than white women. This study aimed to investigate whether baseline and/or change in body fat and its distribution predict type 2 diabetes (T2D) risk in middle-aged black SA women, 13 years later. Methods: We studied 142 black SA women who are the caregivers of the Birth-to-Twenty plus cohort, and who had normal glucose tolerance (NGT) at baseline. At baseline and follow-up, fasting blood samples, basic anthropometry and dual-energy X-ray absorptiometry-derived body composition were measured. At follow-up, an oral glucose tolerance test was completed. The WHO diabetes diagnostic criteria were used to define NGT, impaired fasting glucose (IFG)/impaired glucose tolerance (IGT), impaired glucose metabolism (IGM) and T2D. Results: At follow-up, 64% of participants remained NGT, whereas 25% developed IGM, and 11% developed T2D. The IGM and the T2D groups were combined for statistical analyses. At baseline, trunk fat mass (FM), VAT but not SAT (measures of central FM) were higher in the IGM/T2D group than the NGT group (p < 0.0001). In contrast, the IGM/T2D group had lower leg %FM at baseline than the NGT group (p < 0.0001). Baseline trunk FM (Odds ratio per 1 kg increase (95% confidence interval, 1.95 (1.43-2.67))), and VAT (OR per 10 cm(2) increase, 1.25 (1.10-1.42)), and the change in VAT (1.12 (1.03-1.23)) were associated with greater odds of developing IGM/T2D, whereas baseline leg FM (OR per 1 kg increase, 0.55 (0.41-0.73)) were associated with reduced IGM/T2D risk at follow-up (p < 0.05). Conclusions: Relative fat redistribution, with VAT accumulation, predicted the development of IGM/T2D 13 years before its onset. Prevention of central obesity is a key factor to reduce the risk of developing T2D among middle-aged urban black SA women.

  • 22. Mtintsilana, Asanda
    et al.
    Micklesfield, Lisa K.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Shivappa, Nitin
    Hebert, James R.
    Kengne, Andre P.
    Goedecke, Julia H.
    Adiposity Mediates the Association between the Dietary Inflammatory Index and Markers of Type 2 Diabetes Risk in Middle-Aged Black South African Women2019Inngår i: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, nr 6, artikkel-id 1246Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dietary inflammatory index (DII®), a validated tool used to measure the inflammatory potential of the diet, has been associated with metabolic disorders in various settings, but not in African populations. The aim of this study was to investigate whether the DII is associated with markers of type 2 diabetes (T2D) risk, and if this association is mediated by adiposity and/or low-grade inflammation, in black South Africa women. Energy-adjusted-DII (E-DII) scores were calculated in 190 women (median age, 53 years) from the Birth-to-Twenty plus cohort using a validated food frequency questionnaire. Fasting glucose, insulin, HbA1c, and inflammatory cytokines were measured, and an oral glucose tolerance test performed. Basic anthropometry and dual-energy x-ray absorptiometry-derived body fat, including estimate of visceral adipose tissue (VAT) area, were measured. E-DII scores were associated with all markers of T2D risk, namely, fasting glucose and insulin, HbA1c, HOMA2-IR, two-hour glucose and Matsuda index (all p < 0.05). After adjusting for age, measures of adiposity, but not inflammatory cytokines, mediated the association between E-DII and markers of T2D risk (p < 0.05). Measures of central obesity had proportionally higher (range: 23.5–100%) mediation effects than total obesity (range: 10–60%). The E-DII is associated with T2D risk through obesity, in particular central obesity, among black middle-aged South African women.

  • 23.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Andersson, Tomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Larsson, Christel
    Department of Food and Nutrition, and Sport Science, Goteborgs Universitet, Goteborg, Sweden.
    Holst, Jens Juul
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Postprandial levels of GLP-1, GIP, and glucagon after two years of weight loss with a Paleolithic diet: a randomized controlled trial in healthy obese women2019Inngår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 180, nr 6, s. 417-427Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate how weight loss by different diets impacts on postprandial levels of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon.

    METHODS: In this single-centre, parallel group 2-year trial, 70 healthy postmenopausal obese women were randomized to the Paleolithic diet or a healthy control diet based on Nordic Nutrition Recommendations. Both diets were without calorie restriction. The primary outcome was the change in fat mass. Here, secondary analyses on GLP-1, GIP, and glucagon measured during an OGTT are described.

    RESULTS: In the Paleolithic diet group, mean weight loss compared to baseline was 11% at 6 months, and 10% at 24 months. In the control diet group, mean weight loss was 6% after 6 and 24 months (P = 0.0001 and P = 0.049 for the comparison between groups at 6 and 24 months respectively). Compared to baseline, the mean incremental area under the curve (iAUC) for GLP-1 increased by 34% and 45% after 6 and 24 months in the Paleolithic diet group, and increased by 59% after 24 months in the control diet group. The mean iAUC for GIP increased only in the Paleolithic diet group. The AUC for glucagon increased during the first 6 months in both groups. The fasting glucagon increase correlated with the β-hydroxybutyrate increase.

    CONCLUSIONS: Weight loss caused an increase in postprandial GLP-1 levels and a further rise occurred during weight maintenance. Postprandial GIP levels increased only after the Paleolithic diet. Reduced postprandial glucagon suppression may be caused by a catabolic state.

  • 24. Skärby, Rut
    et al.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ökat om­vårdnadsbehov främsta orsak till lång vårdtid på medicinklinik: Retrospektiv journalstudie styrker att tidig vårdplanering skulle kunna ge bättre platstillgång2014Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 6, s. 219-222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    En retrospektiv journalstudie visar att 50 procent av alla patienter som lades in på medicin­klinik hade en vårdtid <3 dygn och upptog endast 14 procent av de belagda sjukhussängarna.

    24 procent av alla patienter som lades in på medicinklinik hade en vårdtid >5 dygn, vilket upptog 65 procent av de belagda sjukhussängarna.

    Behov av vårdplanering och/eller förändrade heminsatser var den faktor som var starkast kopplad till lång vårdtid. 

    Behov av sjukvårdsinsatser som till stor del är sjukhusbundna (invasiva åtgärder), behov av utredningar (t ex ekokardiografi och röntgen), sjuklighet (t ex hypoalbuminemi, hyponatremi och takykardi) och antibiotikabehandling visade sig i studien vara kopplade till lång vårdtid.

  • 25.
    Thysell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Michael B
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Validated and Predictive Processing of Gas Chromatography-Mass Spectrometry Based Metabolomics Data for Large Scale Screening Studies, Diagnostics and Metabolite Pattern Verification2012Inngår i: Metabolites, ISSN 2218-1989, Vol. 2, s. 796-817Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern. The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern.

  • 26.
    Thysell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Chorell, Elin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Svensson, Michael B.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Moritz, Thomas
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Processing of mass spectrometry based metabolomics data for large scale screening studies and diagnosticsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    In mass spectrometry based metabolomics predictive data processing and sample classification based on representative sample subsets makes it possible to screen large sample banks or data sets in an efficient fashion regarding both data quality and processing time. This is a requirement for making use of high sensitivity and complexity metabolite data and to turn the metabolomics field into a competitive omics platform for biological interpretation and diagnostics. Predictive metabolomics by means of hierarchical multivariate curve resolution (H-MCR) followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for the processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human blood serum samples collected in a study of strenuous physical exercise. The efficiency of the predictive processing as a high throughput tool for generating high quality data is clearly proven and stated as a main benefit of the method. Extensive model validation schemes by means of cross validation and external predictions verified the robustness of the extracted systematic patterns in the data. Comparisons regarding the extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power concerning longitudinal predictions provided proof for the diagnostic potential of the methodology. Finally, the predictive metabolite pattern was interpreted physiologically as well as verified in the literature, highlighting the biological relevance of the diagnostic pattern. The suggested approach makes it feasible to screen large data or sample sets with retained data quality and interpretation and to do this in a high throughput fashion. The method could be of value for sample bank mining, metabolome-wide association studies, verification of marker patterns and development of diagnostic systems.

  • 27.
    Thysell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Validated and predictive processing of gas chromatography-mass spectra screening studies, diagnostics and metabolite pattern verification2012Inngår i: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 2, nr 4, s. 796-817Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern.

  • 28.
    Thysell, Elin
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Pohjanen, Elin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindberg, Johan
    Schuppe-Koistinen, Ina
    Moritz, Thomas
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Reliable Profile Detection in Comparative Metabolomics2007Inngår i: Omics, ISSN 1536-2310, E-ISSN 1557-8100, Vol. 11, nr 2, s. 209-224Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A strategy for processing of metabolomic GC/MS data is presented. By considering the relationship between quantity and quality of detected profiles, representative data suitable for multiple sample comparisons and metabolite identification was generated. Design of experiments (DOE) and multivariate analysis was used to relate the changes in settings of the hierarchical multivariate curve resolution (H-MCR) method to quantitative and qualitative characteristics of the output data. These characteristics included number of resolved profiles, chromatographic quality in terms of reproducibility between analytical replicates, and spectral quality defined by purity and number of spectra containing structural information. The strategy was exemplified in two datasets: one containing 119 common metabolites, 18 of which were varied according to a DOE protocol; and one consisting of rat urine samples from control rats and rats exposed to a liver toxin. It was shown that the performance of the data processing could be optimized to produce metabolite data of high quality that allowed reliable sample comparisons and metabolite identification. This is a general approach applicable to any type of data processing where the important processing parameters are known and relevant output data characteristics can be defined. The results imply that this type of data quality optimization should be carried out as an integral step of data processing to ensure high quality data for further modeling and biological evaluation. Within metabolomics, this degree of optimization will be of high importance to generate models and extract biomarkers or biomarker patterns of biological or clinical relevance.

  • 29.
    Zeng, Yingxu
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Mtintsilana, Asanda
    Goedecke, Julia H.
    Micklesfield, Lisa K.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Alterations in the metabolism of phospholipids, bile acids and branched-chain amino acids predicts development of type 2 diabetes in black South African women: a prospective cohort study2019Inngår i: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 95, s. 57-64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: South Africa (SA) has the highest global projected increase in diabetes risk. Factors typically associated with insulin resistance and type 2 diabetes risk in Caucasians are not significant correlates in black African populations. Therefore, we aimed to identify circulating metabolite patterns that predict type 2 diabetes development in this high-risk, yet understudied SA population.

    Methods: We conducted a prospective cohort study in black SA women with normal glucose tolerance (NGT). Participants were followed for 13 years and developed (i) type 2 diabetes (n = 20, NGT-T2D), (ii) impaired glucose tolerance (IGT) (n = 27, NGT-IGT), or (iii) remained NGT (n = 28, NGT-NGT). Mass-spectrometry based metabolomics and multivariate analyses were used to elucidate metabolite patterns at baseline and at follow-up that were associated with type 2 diabetes development.

    Results: Metabolites of phospholipid, bile acid and branched-chain amino acid (BCAA) metabolism, differed significantly between the NGT-T2D and NGT-NGT groups. At baseline: the NGT-T2D group had i) a higher lysophosphatidylcholine:lysophosphatidylethanolamine ratio containing linoleic acid (LPC(C18:2):LPE(C18:2)), ii) lower proliferation-related bile acids (ursodeoxycholic- and chenodeoxycholic acid), iii) higher levels of leucine and its catabolic intermediates (ketoleucine and C5-carnitine), compared to the NGT-NGT group. At follow-up: the NGT-T2D group had i) lower LPC(C18:2) levels, ii) higher apoptosis-related bile acids (deoxycholic- and glycodeoxycholic acid), and iii) higher levels of all BCAAs and their catabolic intermediates.

    Conclusions: Changes in lysophospholipid metabolism and the bile acid pool occur during the development of type 2 diabetes in black South African women. Further, impaired leucine catabolism precedes valine and isoleucine catabolism in the development of type 2 diabetes. These metabolite patterns can be useful to identify and monitor type 2 diabetes risk >10 years prior to disease onset and provide insight into the pathophysiology of type 2 diabetes in this high risk, but under-studied population.

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