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Mattsson, Cecilia
Publications (10 of 17) Show all publications
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
Open this publication in new window or tab >>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 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, no 5, p. 684-690Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2012
Keywords
IL-8, menopause, gastric bypass surgery
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-51103 (URN)10.1111/j.1365-2265.2011.04322.x (DOI)22168600 (PubMedID)
Available from: 2012-01-10 Created: 2012-01-10 Last updated: 2018-06-08Bibliographically approved
McInnes, K. J., Andersson, T. C., Simonyte, K., Söderström, I., Mattsson, C., Seckl, J. R. & Olsson, T. (2012). Association of 11 beta-hydroxysteroid dehydrogenase type I expression and activity with estrogen receptor beta in adipose tissue from postmenopausal women. Menopause: The Journal of the North American Menopause, 19(12), 1347-1352
Open this publication in new window or tab >>Association of 11 beta-hydroxysteroid dehydrogenase type I expression and activity with estrogen receptor beta in adipose tissue from postmenopausal women
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2012 (English)In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 19, no 12, p. 1347-1352Article in journal (Refereed) Published
Abstract [en]

Objective: 11 beta-Hydroxysteroid dehydrogenase type I (11 beta HSD1) regenerates active cortisol from inert cortisone in adipose tissue. Elevated adipose tissue 11 beta HSD1 activity is observed in obese humans and rodents, where it is linked to obesity and its metabolic consequences. Menopause is also associated with increased abdominal fat accumulation, suggesting that estrogen is also important in adipose tissue metabolism. The purpose of this current study was to establish whether estrogen signaling through estrogen receptor alpha (ER-alpha) and estrogen receptor beta (ER-beta) could influence 11 beta HSD1 in premenopausal and postmenopausal adipose tissues. Methods: Nineteen premenopausal (aged 26 +/- 5 y; body mass index, 23.6 +/- 1.6 kg/m(2)) and 23 postmenopausal (aged 63 +/- 4 y; body mass index, 23.4 +/- 1.9 kg/m(2)) healthy women were studied. Subcutaneous adipose tissue biopsies and fasting venous blood samples were taken. Body composition was measured by bioelectrical impedance analysis. Human Simpson-Golabi-Behmel syndrome adipocyte cells were treated with ER-alpha- and ER-beta-specific agonists for 24 hours. Basic anthropometric data, serum 17 beta-estradiol and progesterone concentrations, ER-alpha and ER-beta messenger RNA (mRNA) levels, and 11 beta HSD1 mRNA, protein, and activity levels were assessed. Results: ER-beta and 11 beta HSD1, but not ER-alpha, mRNAs were significantly increased in adipose tissue from postmenopausal women compared with premenopausal women. ER-beta had a significant positive correlation with the mRNA level of 11 beta HSD1 in adipose tissue from premenopausal and postmenopausal women. This association between ER-beta and 11 beta HSD1 was greatest in adipose tissue from postmenopausal women. In human Simpson-Golabi-Behmel syndrome adipocytes, diarylpropiolnitrile, a selective ER-beta agonist, increased 11 beta HSD1 mRNA, protein, and activity levels. Conclusions: We conclude that, in adipose tissue, ER-beta-mediated estrogen signaling can up-regulate 11 beta HSD1 and that this may be of particular importance in postmenopausal women.

Keywords
Menopause, Estrogen receptor beta, 11 beta-Hydroxysteroid dehydrogenase type I, Adipose tissue
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-63018 (URN)10.1097/gme.0b013e318258aad7 (DOI)000311830800011 ()
Available from: 2013-01-02 Created: 2012-12-27 Last updated: 2018-06-08Bibliographically approved
Dahlqvist, P., Mattsson, C., Olivecrona, Z. & Koskinen, L.-O. D. (2011). Pituitary Function after Severe Traumatic Brain Injury (TBI) in Northern Sweden. In: E Chester Ridway (Ed.), Contents:June 2011, Volume 32, Issue 03_MeetingAbstracts. Paper presented at Endo 2011. the 93rd annual meeting and expo, Endocrine Society Annual Meeting 2011, june 4-7 2011, Boston USA (pp. 396).
Open this publication in new window or tab >>Pituitary Function after Severe Traumatic Brain Injury (TBI) in Northern Sweden
2011 (English)In: Contents:June 2011, Volume 32, Issue 03_MeetingAbstracts / [ed] E Chester Ridway, 2011, p. 396-Conference paper, Published paper (Other academic)
Series
Endocrine Society publishes Endocrine Reviews, ISSN 0163-769X
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-51232 (URN)
Conference
Endo 2011. the 93rd annual meeting and expo, Endocrine Society Annual Meeting 2011, june 4-7 2011, Boston USA
Available from: 2012-01-13 Created: 2012-01-13 Last updated: 2018-06-08Bibliographically approved
Simonyte, K., Olsson, T., Näslund, I., Angelhed, J.-E., Lönn, L., Mattsson, C. & Rask, E. (2010). Weight loss after gastric bypass surgery in women is followed by a metabolically favorable decrease in 11beta-hydroxysteroid dehydrogenase 1 expression in subcutaneous adipose tissue. Journal of Clinical Endocrinology and Metabolism, 95(7), 3527-3531
Open this publication in new window or tab >>Weight loss after gastric bypass surgery in women is followed by a metabolically favorable decrease in 11beta-hydroxysteroid dehydrogenase 1 expression in subcutaneous adipose tissue
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2010 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 7, p. 3527-3531Article in journal (Refereed) Published
Abstract [en]

Weight loss after gastric bypass surgery was followed by metabolically favorable changes in insulin sensitivity, circulating leptin and adiponectin, and peripheral glucocorticoid metabolism. A significant reduction in 11beta-HSD1 expression was observed in sc adipose tissue after weight loss. This suggests that up-regulation of 11beta-HSD1 is a consequence, rather than a cause, of obesity.

Identifiers
urn:nbn:se:umu:diva-41447 (URN)10.1210/jc.2009-2472 (DOI)000279589600062 ()20410231 (PubMedID)
Available from: 2011-03-24 Created: 2011-03-24 Last updated: 2018-06-08Bibliographically approved
Mattsson, C., Reynolds, R. M., Simonyte, K., Olsson, T. & Walker, B. R. (2009). Combined receptor antagonist stimulation of the HPA axis test identifies impaired negative feedback sensitivity to cortisol in obese men. Journal of Clinical Endocrinology and Metabolism, 94(4), 1347-1352
Open this publication in new window or tab >>Combined receptor antagonist stimulation of the HPA axis test identifies impaired negative feedback sensitivity to cortisol in obese men
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2009 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, no 4, p. 1347-1352Article in journal (Refereed) Published
Abstract [en]

Context: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie disorders including obesity, depression, cognitive decline and the metabolic syndrome. Conventional tests of HPA axis negative feedback rely on glucocorticoid receptor (GR) agonists such as dexamethasone, but do not test feedback by endogenous cortisol, potentially mediated by both GR and mineralocorticoid receptors (MR).

Objective: To use a combination of GR (RU38486, mifepristone) and MR (spironolactone) antagonists to explore the poorly understood activation of the HPA axis that occurs in obesity.

Design: Double blind, placebo-controlled randomized cross-over study.

Setting: Clinical research facility.

Participants: 15 lean (BMI 22.0+/-1.6 kg/m(2)) and 16 overweight/obese (BMI 30.1+/-3.5 kg/m(2)) men.

Intervention: Subjects attended on four occasions for blood and saliva sampling every 30 minutes between 1800h and 2200h. At 1100h and 1600h before visits subjects took either 200mg spironolactone, 400mg RU38486, 200mg spironolactone + 400mg RU38486, or placebo orally.

Main outcome measures: serum cortisol levels following drug or placebo.

Results: Cortisol levels did not differ between lean and obese following placebo. Spironolactone and RU38486 alone had modest effects, increasing cortisol by <50% in both groups. However, combined spironolactone plus RU38486 elevated cortisol concentrations substantially, moreso in lean than obese men (2.9(0.3) vs 2.2(0.3) fold elevation, p=0.002).

Conclusions: Combined receptor antagonist stimulation of the HPA axis reveals redundancy of MR and GR in negative feedback in humans. Obese men have impaired responses to combined receptor antagonist stimulation, suggesting impaired negative feedback by endogenous cortisol. Such an approach may be useful to dissect abnormal HPA axis control in neuropsychiatric and other disorders.

Identifiers
urn:nbn:se:umu:diva-19018 (URN)10.1210/jc.2008-2054 (DOI)19141586 (PubMedID)
Available from: 2009-03-03 Created: 2009-03-03 Last updated: 2018-06-09Bibliographically approved
Simonyte, K., Rask, E., Näslund, I., Angelhed, J.-E., Lönn, L., Olsson, T. & Mattsson, C. (2009). Obesity is accompanied by disturbances in peripheral glucocorticoid metabolism and changes in FA recycling. Obesity (Silver Spring, Md.), 17(11), 1982-1987
Open this publication in new window or tab >>Obesity is accompanied by disturbances in peripheral glucocorticoid metabolism and changes in FA recycling
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2009 (English)In: Obesity (Silver Spring, Md.), ISSN 1930-7381, Vol. 17, no 11, p. 1982-1987Article in journal (Refereed) Published
Abstract [en]

The glucocorticoid activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is of major interest in obesity-related morbidity. Alterations in tissue-specific cortisol levels may influence lipogenetic and gluco/glyceroneogenetic pathways in fat and liver. We analyzed the expression and activity of 11betaHSD1 as well as the expression of phosphoenolpyruvate carboxykinase (PEPCK), sterol regulatory element binding protein (SREBP), and fatty acid synthase (FAS) in adipose and liver and investigated putative associations between 11betaHSD1 and energy metabolism genes. A total of 33 obese women (mean BMI 44.6) undergoing gastric bypass surgery were enrolled. Subcutaneous adipose tissue (SAT), omental fat (omental adipose tissue (OmAT)), and liver biopsies were collected during the surgery. 11betaHSD1 gene expression was higher in SAT vs. OmAT (P = 0.013), whereas the activity was higher in OmAT (P = 0.009). The SAT 11betaHSD1 correlated with waist circumference (P = 0.045) and was an independent predictor for the OmAT area in a linear regression model. Energy metabolism genes had AT depot-specific expression; higher leptin and SREBP in SAT than OmAT, but higher PEPCK in OmAT than SAT. The expression of 11betaHSD1 correlated with PEPCK in both AT depots (P = 0.05 for SAT and P = 0.0001 for OmAT). Hepatic 11betaHSD1 activity correlated negatively with abdominal adipose area (P = 0.002) and expression positively with PEPCK (P = 0.003). In human obesity, glucocorticoid regeneration in the SAT is associated with central fat accumulation indicating that the importance of this specific fat depot is underestimated. Central fat accumulation is negatively associated with hepatic 11betaHSD1 activity. A disturbance in peripheral glucocorticoid metabolism is associated with changes in genes involved in fatty acid (FA) recycling in adipose tissue (AT).

Identifiers
urn:nbn:se:umu:diva-32385 (URN)10.1038/oby.2009.99 (DOI)19360009 (PubMedID)
Available from: 2010-03-10 Created: 2010-03-10 Last updated: 2018-06-08Bibliographically approved
Homer, N. Z., Reynolds, R. M., Mattsson, C., Bailey, M. A., Walker, B. R. & Andrew, R. (2009). Quantitative analysis of RU38486 (mifepristone) by HPLC triple quadrupole mass spectrometry. Journal of chromatography. B, 877(5-6), 497-501
Open this publication in new window or tab >>Quantitative analysis of RU38486 (mifepristone) by HPLC triple quadrupole mass spectrometry
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2009 (English)In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 877, no 5-6, p. 497-501Article in journal (Refereed) Published
Abstract [en]

A sensitive liquid chromatography-mass spectrometric method was validated for the quantification of RU38486 (mifepristone) in human and murine plasma. The analyte and internal standard (alfaxolone) were extracted by liquid-liquid extraction with diethyl ether, resolved on a C18 column using gradient elution with methanol and ammonium acetate and detected after positive electrospray ionization (m/z 430-->372; m/z 333-->297, respectively). Quantification was linear over the range 0.5-500ng (r(2)>0.997), precise and accurate (intra-assay RSD</=7.2%, RME</=8.2%; inter-assay RSD</=15.7% RME</=10.2%). The limit of quantification (LOQ) was 50pg injected on column, permitting reproducible analysis of RU38486 in small volumes of plasma.

National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-19077 (URN)10.1016/j.jchromb.2008.12.051 (DOI)19157997 (PubMedID)
Available from: 2009-03-04 Created: 2009-03-04 Last updated: 2018-06-09Bibliographically approved
Andersson, T., Simonyte, K., Andrew, R., Strand, M., Burén, J., Walker, B. R., . . . Olsson, T. (2009). Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women. PloS one, 4(12), e8475
Open this publication in new window or tab >>Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women
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2009 (English)In: PloS one, ISSN 1932-6203, Vol. 4, no 12, p. e8475-Article in journal (Refereed) Published
Abstract [en]

With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05). Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion), suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

Identifiers
urn:nbn:se:umu:diva-32457 (URN)10.1371/journal.pone.0008475 (DOI)20041117 (PubMedID)
Available from: 2010-03-11 Created: 2010-03-11 Last updated: 2018-06-08Bibliographically approved
Mattsson, C. & Olsson, T. (2007). Estrogens and glucocorticoid hormones in adipose tissue metabolism. Current Medicinal Chemistry, 27, 2918-24
Open this publication in new window or tab >>Estrogens and glucocorticoid hormones in adipose tissue metabolism
2007 (English)In: Current Medicinal Chemistry, ISSN 0929-8673, Vol. 27, p. 2918-24Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-5790 (URN)
Available from: 2007-11-30 Created: 2007-11-30 Last updated: 2018-06-09Bibliographically approved
Mattsson, C., Rask, E., Carlström, K., Andersson, J., Eliasson, M., Ahrén, B., . . . Olsson, T. (2007). Gender-specific links between hepatic 11beta reduction of cortisone and adipokines. Obesity, 15(4), 887-894
Open this publication in new window or tab >>Gender-specific links between hepatic 11beta reduction of cortisone and adipokines
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2007 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 15, no 4, p. 887-894Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Reduction of cortisone to cortisol is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-alpha (TNF-alpha), are of importance for 11betaHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-alpha receptors and/or sex hormones. RESEARCH METHODS AND PROCEDURES: A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11betaHSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol. RESULTS: Hepatic 11betaHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-alpha receptors also after adjustment of BMI and waist circumference. In contrast, 11beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference. DISCUSSION: Hepatic 11beta reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11betaHSD1 in both genders.

Keywords
11-beta-Hydroxysteroid Dehydrogenase Type 1/*metabolism, Adipose Tissue/*metabolism, Adult, Cortisone/*metabolism, Cytokines/*metabolism, Female, Gene Expression Regulation, Humans, Insulin/metabolism, Leptin/metabolism, Liver/metabolism, Male, Middle Aged, Sex Factors, Tumor Necrosis Factor-alpha/metabolism
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-16341 (URN)10.1038/oby.2007.587 (DOI)000245729300014 ()17426324 (PubMedID)
Available from: 2007-09-12 Created: 2007-09-12 Last updated: 2018-12-28Bibliographically approved
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