umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Sjödin, Kotryna Simonyte
Alternative names
Publications (10 of 16) Show all publications
Sjödin, K. S., Domellöf, M., Lagerqvist, C., Hernell, O., Lönnerdal, B., Szymlek-Gay, E. A., . . . Lind, T. (2019). Administration of ferrous sulfate drops has significant effects on the gut microbiota of iron-sufficient infants: a randomised controlled study [Letter to the editor]. Gut, 68(11)
Open this publication in new window or tab >>Administration of ferrous sulfate drops has significant effects on the gut microbiota of iron-sufficient infants: a randomised controlled study
Show others...
2019 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 11Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-167039 (URN)10.1136/gutjnl-2018-316988 (DOI)000497817400023 ()30343273 (PubMedID)
Funder
Västerbotten County Council
Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2020-01-09Bibliographically approved
Simonyté Sjödin, K., Hammarström, M.-L., Rydén, P., Sjödin, A., Hernell, O., Engstrand, L. & West, C. E. (2019). Temporal and long-term gut microbiota variation in allergic disease: a prospective study from infancy to school age. Allergy. European Journal of Allergy and Clinical Immunology, 74(1), 176-185
Open this publication in new window or tab >>Temporal and long-term gut microbiota variation in allergic disease: a prospective study from infancy to school age
Show others...
2019 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 74, no 1, p. 176-185Article in journal (Refereed) Published
Abstract [en]

Background: Compositional changes in the early‐life gut microbiota have been implicated in IgE‐associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE‐associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T‐cell regulation, estimated as responses to polyclonal T‐cell activation.

Methods: Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL‐10 and FOXP3 mRNA copies were determined using real‐time quantitative reverse transcriptase‐PCR.

Results: At 8 years of age, 21 children were diagnosed with IgE‐associated allergic disease and 90% displayed allergic comorbidity. Seventy‐two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8‐year‐olds was enriched in Bifidobacteriumand depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8‐year-olds, Faecalibacterium correlated with IL‐10 mRNA levels (rs = 0.49, Padj = 0.02) with the same trend for FOXP3 (rs = 0.39, Padj = 0.08).

Conclusions: We identified both temporal and long‐term variation in the differential abundance of specific bacterial genera in children developing IgE‐associated allergic disease. Improved dietary interventions aiming at expanding immune‐modulatory taxa could be studied for prevention of allergic disease.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
allergy, diversity, intestinal colonization, microbiome, T-cell response
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-157612 (URN)10.1111/all.13485 (DOI)000459664100017 ()29786876 (PubMedID)
Available from: 2019-03-27 Created: 2019-03-27 Last updated: 2019-03-27Bibliographically approved
Sjödin, K. S., Vidman, L., Rydén, P. & West, C. E. (2016). Emerging evidence of the role of gut microbiota in the development of allergic diseases. Current Opinion in Allergy and Clinical Immunology, 16(4), 390-395
Open this publication in new window or tab >>Emerging evidence of the role of gut microbiota in the development of allergic diseases
2016 (English)In: Current Opinion in Allergy and Clinical Immunology, ISSN 1528-4050, E-ISSN 1473-6322, Vol. 16, no 4, p. 390-395Article, review/survey (Refereed) Published
Abstract [en]

Purpose of review The purpose is to review recent studies examining the role of gut microbiota in allergic diseases and asthma.

Recent findings Work in experimental models gives further evidence that a disturbed gut microbiota influences the propensity to develop allergic manifestations, and that changing the gut microbiota by dietary means (high fiber/acetate or prebiotics) in pregnancy may reduce the risk of allergic airways disease and food allergy in the offspring, respectively. The gut microbiome in established allergic disease and prior to disease onset has also been assessed in clinical trials. One study demonstrated a strong association between high abundance of Faecalibacterium prausnitzii and decreased levels of butyrate and propionate, and established eczema. Lower relative abundance of Ruminococcaceae appears to be implicated in food sensitization and to precede the development of atopic eczema. Decreased relative abundance of Lachnospira, Veillonella, Faecalibacterium, and Rothia in early infancy was reported to be associated with increased asthma risk. Inoculation of germ-free mice with these genera decreased airway inflammation in their offspring thereby proposing a causal role of bacteria in preventing allergic airways disease.

Summary Gut microbiome research is an actively developing field. Although candidate bacterial taxa have been reported it still remains unclear which bacteria (or other microbes), in which numbers and combinations, and when during the gut colonization process may prevent allergic diseases and asthma. There is still a call for standardized approaches that will enable direct comparison of different studies.

Keywords
allergic disease, asthma, biodiversity, gut microbiome, homeostasis, immunity
National Category
Immunology in the medical area Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-124315 (URN)10.1097/ACI.0000000000000277 (DOI)000379587800015 ()
External cooperation:
Available from: 2016-09-06 Created: 2016-08-04 Last updated: 2018-06-07Bibliographically approved
Stomby, A., Simonyte, K., Mellberg, C., Ryberg, M., Stimson, R. H., Larsson, C., . . . Olsson, T. (2015). Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women. International Journal of Obesity, 39(5), 814-819
Open this publication in new window or tab >>Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women
Show others...
2015 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 39, no 5, p. 814-819Article in journal (Refereed) Published
Abstract [en]

Background/Objectives: Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women.

Subjects/Methods: Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied.

Results: Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11βHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months.

Conclusions: Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-96782 (URN)10.1038/ijo.2014.188 (DOI)000354097900013 ()25349058 (PubMedID)
Available from: 2014-12-03 Created: 2014-12-03 Last updated: 2018-06-07Bibliographically approved
Rojo, M. L., Cipriano, M., Söderstrom, I., Simonyte, K., Olsson, T. & Fowler, C. J. (2014). Effects of dietary glucose and fructose upon cannabinoid CB1 receptor functionality in the rat brain: a pilot study. Life Sciences, 108(2), 116-121
Open this publication in new window or tab >>Effects of dietary glucose and fructose upon cannabinoid CB1 receptor functionality in the rat brain: a pilot study
Show others...
2014 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 108, no 2, p. 116-121Article in journal (Refereed) Published
Abstract [en]

Aims: A high consumption of fructose leads not only to peripheral changes in insulin sensitivity and vascular function, but also to central changes in several brain regions. Given the role of the endogenous cannabinoid system in the control of energy intake, we undertook a pilot study to determine whether a high fructose diet produced changes in brain CB1 receptor functionality. Main methods: Male rats given access ad libitum to normal chow were given either water, glucose or fructose solutions to drink. CBI receptor functionality was measured autoradiographically as the increase in [35SJGTP)/S binding produced by the agonist CP55,940. Key findings: Seven regions were investigated: the prefrontal cortex, caudate-putamen, hippocampal CAI-CA3, dentate gyrus, amygdala, and dorsomedial and ventromedial hypothalami. Two-way robust Wilcoxon analyses for each brain region indicated that the dietary treatment did not produce significant main effects upon agonist-stimulated [35S]GThyS binding in any of the regions, in contrast to a significant main effect upon both leptin and adiponectin levels in the blood. However, a MANCOVA of the data controlling for leptin and adiponectin as co-variables identified a significant effect of glucose and fructose treatment for five weeks upon the [35S]GTPI/S response in the ventromedial hypothalamus, a region of importance for regulation of appetite. Significance: It is concluded from this pilot study that palatable solutions do not produce overt changes in brain CBI receptor functionality, although subtle changes in discrete brain regions may occur.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Fructose, Endocannabinoid, fructose, endocannabinoid, CB1 receptors, [S-35]GTP gamma S autoradiography, leptin, adiponectin
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:umu:diva-91832 (URN)10.1016/j.lfs.2014.05.019 (DOI)000339367100008 ()
Available from: 2014-09-01 Created: 2014-08-18 Last updated: 2018-06-07Bibliographically approved
Rask, E., Simonyte, K., Lönn, L. & Axelson, M. (2013). Cortisol metabolism after weight loss: associations with 11 beta-HSD type 1 and markers of obesity in women. Clinical Endocrinology, 78(5), 700-705
Open this publication in new window or tab >>Cortisol metabolism after weight loss: associations with 11 beta-HSD type 1 and markers of obesity in women
2013 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 78, no 5, p. 700-705Article in journal (Refereed) Published
Abstract [en]

Objective Increased glucocorticoid metabolite excretion and enhanced expression and activity of 11-hydroxysteroid dehydrogenase type 1 in adipose tissue are closely correlated with obesity and its detrimental consequences. Weight loss ameliorates the latter. The aim of this study was to explore whether increased glucocorticoid exposure in obesity is improved with substantial weight loss and thus is a consequence rather than a cause of obesity. Design and patients A prospective cohort study in 31 women. Measurements 11-HSD type 1 expression and activity, urinary glucocorticoid metabolite excretion, body composition including regional adipose tissue depots and insulin resistance by HOMA-IR before and 2years after gastric bypass surgery. Results After weight loss, excretion of cortisol and cortisone metabolites decreased. Both cortisol and cortisone metabolite excretion correlated with central obesity, where the intraabdominal fat depot showed the strongest association. Cortisol metabolites correlated with 11-HSD type 1 activity in abdominal subcutaneous adipose tissue. The ratio of cortisol to cortisone metabolites [(5-tetrahydrocortisol (5THF)+tetrahydrocortisol (THF)+-cortol)/(tetrahydrocortisone (THE)+-cortolone)] and the ratio of 5-THF/THF both decreased after stable weight loss, reflecting a downregulation of the net activities of 11-HSD type 1 and 5-reductase. Conclusion Long-term weight loss in women is not only followed by reduced glucocorticoid production, but also favourably decreases the global and tissue-specific activity of the cortisol-activating enzyme 11 -HSD type 1, possibly contributing to the health benefits of bariatric surgery.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-71078 (URN)10.1111/j.1365-2265.2012.04333.x (DOI)000317615300010 ()
Available from: 2013-06-17 Created: 2013-05-20 Last updated: 2018-06-08Bibliographically approved
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
Show others...
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
Show others...
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
Simonyté, K. (2011). Alterations in peripheral glucocorticoid metabolism: effects of weight changes. (Doctoral dissertation). Umeå: Umeå university
Open this publication in new window or tab >>Alterations in peripheral glucocorticoid metabolism: effects of weight changes
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: An important role has been suggested for tissue-specific glucocorticoid metabolism in the development of obesity and its complications. 11ß hydroxysteroid dehydrogenase 1 (11ßHSD1) is an enzyme that catalyzes the interconversion of biologically inactive cortisone to active cortisol, thereby regulating its access to glucocorticoid receptors in target tissues. Indeed, an unfavorable metabolic outcome has been associated with increased 11ßHSD1 gene expression and activity in adipose tissue and liver in humans and rodents. Cortisol is an important regulator of phosphoenolpyruvate carboxykinase (PEPCK) a key enzyme in gluconeogenesis and lipid metabolism. In rodents, overexpression of PEPCK in adipose tissue leads to adiposity and increased fatty acid re-esterification. In human obesity, PEPCK has been positively associated with body fat, total cholesterol levels, and plasma triglycerides. However, few studies have addressed the putative reversibility of peripheral cortisol levels and disturbed fatty acid homeostasis that may accompany weight loss. The aim of this thesis was to investigate alterations in peripheral glucocorticoid metabolism in the context of obesity, and putative modulations of glucocorticoid metabolism in the context of weight changes in humans and rodents.

Materials & Methods: 11ßHSD1 expression/activity in different adipose tissue depots and liver, the expression of genes involved in adipogenesis and fatty acid homeostasis, and serum levels of adipose tissue-derived adipokines were investigated in severely obese women before and after surgically induced weight loss. The same parameters were measured in female Sprague-Dawley rats fed on high-fat and control diets.

Results: In severely obese women, 11ßHSD1 expression was higher in subcutaneous adipose tissue (SAT), while 11ßHSD1 activity and PEPCK expression were higher in the omental depot. In a multivariate analysis, SAT 11ßHSD1 activity was an independent predictor for central fat accumulation. Hepatic 11ßHSD1 activity and levels of intra-abdominal fat storage correlated negatively, while 11ßHSD1 correlated positively with PEPCK in adipose tissue and liver. Weight loss after gastric bypass surgery was followed by significant and metabolically beneficial reductions in subcutaneous 11ßHSD1 and leptin gene expression, as well as reduced circulating leptin and increased adiponectin levels. In contrast, PEPCK gene expression did not change with weight loss. In rats, a high-fat diet did not affect body weight, but was associated with increased serum leptin and decreased adiponectin levels. Short-term, high-fat diet feeding resulted in the up-regulation of SAT 11ßHSD1 expression, while chronic feeding led to its significant down-regulation (compared with the control diet and short-term, high-fat feeding). Interestingly, hepatic 11ßHSD1 expression was constantly downregulated in rats that were fed a high-fat diet.

Conclusions: Severe obesity in women was accompanied by a metabolically adverse increase of 11ßHSD1 in adipose tissue, with a concomitant decrease in the liver. Subcutaneous 11ßHSD1 was an independent predictor for central fat accumulation. As weight loss was followed by significant down-regulation of subcutaneous 11ßHSD1, we suggest that up-regulation of this enzyme was a consequence, rather than a cause of obesity. In rodents, a high-fat diet induced dynamic changes in 11ßHSD1 in SAT and liver, both being down-regulated after chronic high-fat feeding without altered weight. In summary, weight changes and alterations in fat and liver glucocorticoid metabolism are closely linked. Moreover, a high-fat diet significantly influences 11ßHSD1 expression/activity in adipose tissue and liver without affecting body weight.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2011. p. 44
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1418
Keywords
11ß Hydroxysteroid dehydrogenase 1, obesity, glucocorticoids, cortisol, phosphoenolpyruvate carboxykinase, adipose tissue, liver
National Category
Endocrinology and Diabetes
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-43160 (URN)978-91-7459-192-7 (ISBN)
Public defence
2011-05-13, Hörsal Betula, NUS, By 6M, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2011-04-21 Created: 2011-04-20 Last updated: 2018-06-08Bibliographically approved
Andersson, T., Söderström, I., Simonyté, K. & Olsson, T. (2010). Estrogen reduces 11beta-hydroxysteroid dehydrogenase type 1 in liver and visceral, but not subcutaneous, adipose tissue in rats. Obesity (Silver Spring, Md.), 18(3), 470-475
Open this publication in new window or tab >>Estrogen reduces 11beta-hydroxysteroid dehydrogenase type 1 in liver and visceral, but not subcutaneous, adipose tissue in rats
2010 (English)In: Obesity (Silver Spring, Md.), ISSN 1930-7381, Vol. 18, no 3, p. 470-475Article in journal (Refereed) Published
Abstract [en]

Following menopause, body fat is redistributed from peripheral to central depots. This may be linked to the age related decrease in estrogen levels. We hypothesized that estrogen supplementation could counteract this fat redistribution through tissue-specific modulation of glucocorticoid exposure. We measured fat depot masses and the expression and activity of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in fat and liver of ovariectomized female rats treated with or without 17beta-estradiol. 11betaHSD1 converts inert cortisone, or 11-dehydrocorticosterone in rats into active cortisol and corticosterone. Estradiol-treated rats gained less weight and had significantly lower visceral adipose tissue weight than nontreated rats (P < 0.01); subcutaneous adipose weight was unaltered. In addition, 11betaHSD1 activity/expression was downregulated in liver and visceral, but not subcutaneous, fat of estradiol-treated rats (P < 0.001 for both). This downregulation altered the balance of 11betaHSD1 expression and activity between adipose tissue depots, with higher levels in subcutaneous than visceral adipose tissue of estradiol-treated animals (P < 0.05 for both), opposite the pattern in ovariectomized rats not treated with estradiol (P < 0.001 for mRNA expression). Thus, estrogen modulates fat distribution, at least in part, through effects on tissue-specific glucocorticoid metabolism, suggesting that estrogen replacement therapy could influence obesity related morbidity in postmenopausal women.

Identifiers
urn:nbn:se:umu:diva-30991 (URN)10.1038/oby.2009.294 (DOI)19763091 (PubMedID)
Available from: 2010-01-26 Created: 2010-01-26 Last updated: 2018-06-08Bibliographically approved
Organisations

Search in DiVA

Show all publications