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Alvehus, Malin
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Blomquist, C., Alvehus, M., Burén, J., Ryberg, M., Larsson, C., Lindahl, B., . . . Olsson, T. (2017). Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity. Obesity, 25(5), 892-900
Öppna denna publikation i ny flik eller fönster >>Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity
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2017 (Engelska)Ingår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 25, nr 5, s. 892-900Artikel i tidskrift (Refereegranskat) Published
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.

Nationell ämneskategori
Näringslära
Identifikatorer
urn:nbn:se:umu:diva-134986 (URN)10.1002/oby.21815 (DOI)000400045000013 ()28440046 (PubMedID)
Forskningsfinansiär
Vetenskapsrådet, K2011-12237-15-6
Tillgänglig från: 2017-05-15 Skapad: 2017-05-15 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Alvehus, M., Boman, N., Söderlund, K., Svensson, M. B. & Buren, J. (2014). Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training. European Journal of Applied Physiology, 114(7), 1463-1471
Öppna denna publikation i ny flik eller fönster >>Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training
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2014 (Engelska)Ingår i: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 114, nr 7, s. 1463-1471Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The effects of resistance training on mitochondrial biogenesis and oxidative capacity in skeletal muscle are not fully characterized, and even less is known about alterations in adipose tissue. We aimed to investigate adaptations in oxidative metabolism in skeletal muscle and adipose tissue after 8 weeks of heavy resistance training in apparently healthy young men. Expression of genes linked to oxidative metabolism in the skeletal muscle and adipose tissue was assessed before and after the training program. Body composition, peak oxygen uptake (VO2 peak), fat oxidation, activity of mitochondrial enzyme in muscle, and serum adiponectin levels were also determined before and after resistance training. In muscle, the expression of the genes AdipoR1 and COX4 increased after resistance training (9 and 13 %, respectively), whereas the expression levels of the genes PGC-1 alpha, SIRT1, TFAM, CPT1b, and FNDC5 did not change. In adipose tissue, the expression of the genes SIRT1 and CPT1b decreased after training (20 and 23 %, respectively). There was an increase in lean mass (from 59.7 +/- A 6.1 to 61.9 +/- A 6.2 kg), VO2 peak (from 49.7 +/- A 5.5 to 56.3 +/- A 5.0 ml/kg/min), and fat oxidation (from 6.8 +/- A 2.1 to 9.1 +/- A 2.7 mg/kg fat-free mass/min) after training, whereas serum adiponectin levels decreased significantly and enzyme activity of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase did not change. Despite significant increases in VO2 peak, fat oxidation, and lean mass following resistance training, the total effect on gene expression and enzyme activity linked to oxidative metabolism was moderate.

Nyckelord
Resistance training, Oxidative capacity, Skeletal muscle, Adipose tissue, Gene expression, Enzyme activity
Nationell ämneskategori
Idrottsvetenskap
Identifikatorer
urn:nbn:se:umu:diva-91051 (URN)10.1007/s00421-014-2879-9 (DOI)000337052300013 ()
Tillgänglig från: 2014-07-11 Skapad: 2014-07-10 Senast uppdaterad: 2018-06-07Bibliografiskt granskad
Alvehus, M., Simonyte, K., Andersson, T., Söderström, I., Burén, J., Rask, E., . . . Olsson, T. (2012). Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women. Clinical Endocrinology, 77(5), 684-690
Öppna denna publikation i ny flik eller fönster >>Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women
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2012 (Engelska)Ingår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 5, s. 684-690Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective:  The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease which are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared to premenopausal women. We also wanted to determine if these markers are reduced by stable weight loss in obese women. Design and methods:  Anthropometric data, blood samples, and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated. Results:  IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal versus premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal versus premenopausal women. Two years after gastric bypass surgery, adipose expression of IL-8, tumor necrosis factor-α, and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before gastric bypass surgery, but these associations disappeared after surgery. Conclusion:  Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss. © 2011 Blackwell Publishing Ltd.

Ort, förlag, år, upplaga, sidor
Wiley-Blackwell, 2012
Nyckelord
IL-8, menopause, gastric bypass surgery
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:umu:diva-51103 (URN)10.1111/j.1365-2265.2011.04322.x (DOI)22168600 (PubMedID)
Tillgänglig från: 2012-01-10 Skapad: 2012-01-10 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Alvehus, M. (2012). Obesity-associated inflammation in adipose tissue. (Doctoral dissertation). Umeå: Umeå University
Öppna denna publikation i ny flik eller fönster >>Obesity-associated inflammation in adipose tissue
2012 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Background: Excess body fat, particularly in the visceral depot, is linked to increased mortality and morbidity, including the development of diseases such as type 2 diabetes, cardiovascular disease, and cancer. Chronic low-grade inflammation in adipose tissue may be a key mediator of obesity-associated diseases. Importantly, specific pro-inflammatory cytokines have been shown to influence adipose tissue function and could therefore be a link to metabolic disorders. Circulating cytokine levels may also be increased in obesity and metabolic diseases. However, although fat distribution and inflammation are clearly linked to metabolic disorders, inflammatory gene expression in the different abdominal adipose depots has not been investigated in detail. The menopausal transition is followed by a centralization of body fat and increased adiposity. Notably, inflammatory changes in fat during the menopausal transition have not been characterized. Finally, there is a lack of studies investigating the long-term effects of weight loss on low-grade inflammation. The aim of this thesis was to characterize differences between fat depots and investigate putative changes in low-grade inflammation in adipose tissue and circulation following menopause or weight loss.

Materials & Methods: The expression of inflammation-related genes was investigated in abdominal adipose tissue depots obtained from women with varying adiposity, before and after menopause or weight loss induced by surgery or dietary intervention. Circulating cytokine levels were analyzed using immunoassays.

Results: Visceral fat displayed a distinct and adverse inflammatory profile compared with subcutaneous adipose tissues, and the higher gene expression in visceral fat was associated with adiposity. Postmenopausal women exhibited a higher expression of pro-inflammatory genes than premenopausal women that associated with central fat accumulation. There was also a menopause-related increase in circulating cytokine levels in postmenopausal women. After surgery-induced weight loss, there was a dramatic reduction in inflammatory gene expression followed by increased insulin sensitivity. We observed no alterations in circulating cytokine levels. Long-term dietary intervention, associated with weight loss, had favorable effects on inflammation in both adipose tissue and serum.

Conclusion: Fat accumulation is linked to low-grade inflammation in abdominal adipose tissue. The unique inflammatory pattern of visceral fat suggests a distinct role in adipose tissue inflammation that is aggravated with increasing adiposity. In postmenopausal women, the adverse adipose inflammatory profile was associated with central fat accumulation, while higher circulating cytokine levels correlated with menopausal state/age. Our data from severely obese women undergoing surgery-induced weight loss clearly supports a link between adipose inflammation and insulin resistance. The long-term beneficial effects of weight loss were also demonstrated by the improved inflammatory profile after dietary intervention. In summary, excess body fat is clearly linked to adipose tissue inflammation. Long-term weight loss is accompanied by improved metabolic profile and reduced low-grade inflammation in fat.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2012. s. 57
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1486
Nyckelord
adipose tissue, inflammation, pro-inflammatory cytokines, serum, obesity, weight loss, menopause
Nationell ämneskategori
Allmänmedicin
Identifikatorer
urn:nbn:se:umu:diva-53472 (URN)978-91-7459-388-4 (ISBN)
Disputation
2012-04-27, Sal E04, by 6E, Norrlands universitetssjukhus, Umeå, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2012-04-05 Skapad: 2012-03-28 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Rodriguez-Gaztelumendi, A., Alvehus, M., Andersson, T. & Jacobsson, S. (2011). Comparison of the effects of nicotine upon the transcellular electrical resistance and sucrose permeability of human ECV304/rat C6 co-cultures and human CaCo2 cells. Toxicology Letters, 207(1), 1-6
Öppna denna publikation i ny flik eller fönster >>Comparison of the effects of nicotine upon the transcellular electrical resistance and sucrose permeability of human ECV304/rat C6 co-cultures and human CaCo2 cells
2011 (Engelska)Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 207, nr 1, s. 1-6Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

It is now well established that nicotine adversely affects the integrity of the blood–brain barrier (BBB). In contrast, nicotine has been reported to increase the transendothelial electrical resistance (TEER) of CaCo2 colon cancer cells. In the present study, the effects of nicotine upon the TEER and sucrose permeability of ECV304/C6 co-cultures and, for comparative purposes, CaCo2 cells has been investigated. Neither ECV304 nor C6 cells were found to express measurable membrane levels of nicotinic acetylcholine receptors, as assessed by [3H]–epibatidine binding. Nicotine treatment (0.01–1 µM) for up to 48 h had little or no effect upon the TEER or sucrose permeability of either ECV304/C6 co-cultures or CaCo2 cells. It is concluded that in contrast to the situation for the BBB, ECV304 cells lack nicotinic acetylcholine receptors and the barrier properties of ECV304/C6 co-cultures are not affected to any important extent by nicotine. This study underlines the conclusions made by other authors that the ECV304/C6 co-culture system is of limited validity as a model of the BBB.

Ort, förlag, år, upplaga, sidor
Elsevier Ireland Ltd., 2011
Nyckelord
Nicotine, In vitro blood–brain barrier model, TEER, Sucrose permeability
Nationell ämneskategori
Farmakologi och toxikologi
Forskningsämne
toxikologi
Identifikatorer
urn:nbn:se:umu:diva-47573 (URN)10.1016/j.toxlet.2011.08.014 (DOI)21889975 (PubMedID)
Tillgänglig från: 2011-09-23 Skapad: 2011-09-23 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Evans, J., Goedecke, J. H., Söderström, I., Burén, J., Alvehus, M., Blomquist, C., . . . Olsson, T. (2011). Depot- and ethnic-specific differences in the relationship between adipose tissue inflammation and insulin sensitivity. Clinical Endocrinology, 74(1), 51-59
Öppna denna publikation i ny flik eller fönster >>Depot- and ethnic-specific differences in the relationship between adipose tissue inflammation and insulin sensitivity
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2011 (Engelska)Ingår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 74, nr 1, s. 51-59Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective  It is unclear whether there are differences in inflammatory gene expression between abdominal and gluteal subcutaneous adipose tissue (SAT), and between black and white women. We therefore tested the hypotheses that SAT inflammatory gene expression is greater in the abdominal compared to the gluteal depot, and SAT inflammatory gene expression is associated with differential insulin sensitivity (S(I) ) in black and white women.

Design and methods  S(I) (frequently sampled intravenous glucose tolerance test) and abdominal SAT and gluteal SAT gene expression levels of 13 inflammatory genes were measured in normal-weight (BMI 18-25 kg/m(2) ) and obese (BMI >30 kg/m(2) ) black (n = 30) and white (n = 26) South African women.

Results  Black women had higher abdominal and gluteal SAT expression of CCL2, CD68, TNF-α and CSF-1 compared to white women (P < 0·01). Multivariate analysis showed that inflammatory gene expression in the white women explained 56·8% of the variance in S(I) (P < 0·005), compared to 20·9% in black women (P = 0·30). Gluteal SAT had lower expression of adiponectin, but higher expression of inflammatory cytokines, macrophage markers and leptin than abdominal SAT depots (P < 0·05).

Conclusions  Black South African women had higher inflammatory gene expression levels than white women; however, the relationship between AT inflammation and S(I) was stronger in white compared to black women. Further research is required to explore other factors affecting S(I) in black populations. Contrary to our original hypothesis, gluteal SAT had a greater inflammatory gene expression profile than abdominal SAT depots. The protective nature of gluteo-femoral fat therefore requires further investigation.

Identifikatorer
urn:nbn:se:umu:diva-38726 (URN)10.1111/j.1365-2265.2010.03883.x (DOI)20874774 (PubMedID)
Tillgänglig från: 2010-12-23 Skapad: 2010-12-23 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Alvehus, M., Burén, J., Sjöström, M., Goedecke, J. & Olsson, T. (2010). The human visceral fat depot has a unique inflammatory profile. Obesity, 18(5), 879-883
Öppna denna publikation i ny flik eller fönster >>The human visceral fat depot has a unique inflammatory profile
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2010 (Engelska)Ingår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 18, nr 5, s. 879-883Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Obesity can be considered as a low-grade inflammatory condition, strongly linked to adverse metabolic outcomes. Obesity-associated adipose tissue inflammation is characterized by infiltration of macrophages and increased cytokine and chemokine production. The distribution of adipose tissue impacts the outcomes of obesity, with the accumulation of fat in visceral adipose tissue (VAT) and deep subcutaneous adipose tissue (SAT), but not superficial SAT, being linked to insulin resistance. We hypothesized that the inflammatory gene expression in deep SAT and VAT is higher than in superficial SAT. A total of 17 apparently healthy women (BMI: 29.3 +/- 5.5 kg/m2) were included in the study. Body fat (dual-energy X-ray absorptiometry) and distribution (computed tomography) were measured, and insulin sensitivity, blood lipids, and blood pressure were determined. Inflammation-related differences in gene expression(real-time PCR) from VAT, superficial and deep SAT biopsies were analyzed using univariate and multivariate data analyses. Using multivariate discrimination analysis, VAT appeared as a distinct depot in adipose tissue inflammation,while the SAT depots had a similar pattern, with respect to gene expression. A significantly elevated (P < 0.01)expression of the CC chemokine receptor 2 (CCR2) and macrophage migration inhibitory factor (MIF) in VAT contributed strongly to the discrimination. In conclusion, the human adipose tissue depots have unique inflammatory patterns, with CCR2 and MIF distinguishing between VAT and the SAT depots.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2010
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:umu:diva-34276 (URN)10.1038/oby.2010.22 (DOI)000277234800006 ()20186138 (PubMedID)
Tillgänglig från: 2010-05-24 Skapad: 2010-05-24 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Alvehus, M., Ryberg, M., Blomquist, C., Larsson, C., Lindahl, B., Sandberg, S., . . . Olsson, T.Decreased TLR4 and Increased MIF Adipose Gene Expression Following Long-Term Diet Intervention.
Öppna denna publikation i ny flik eller fönster >>Decreased TLR4 and Increased MIF Adipose Gene Expression Following Long-Term Diet Intervention
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:umu:diva-53465 (URN)
Tillgänglig från: 2012-03-27 Skapad: 2012-03-27 Senast uppdaterad: 2018-06-08
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