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Obesity-associated inflammation in adipose tissue
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2012. , 57 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1486
Keyword [en]
adipose tissue, inflammation, pro-inflammatory cytokines, serum, obesity, weight loss, menopause
National Category
Family Medicine
Identifiers
URN: urn:nbn:se:umu:diva-53472ISBN: 978-91-7459-388-4 (print)OAI: oai:DiVA.org:umu-53472DiVA: diva2:512526
Public defence
2012-04-27, Sal E04, by 6E, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-04-05 Created: 2012-03-28 Last updated: 2012-04-05Bibliographically approved
List of papers
1. The human visceral fat depot has a unique inflammatory profile
Open this publication in new window or tab >>The human visceral fat depot has a unique inflammatory profile
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2010 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 18, no 5, 879-883 p.Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2010
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-34276 (URN)10.1038/oby.2010.22 (DOI)000277234800006 ()20186138 (PubMedID)
Available from: 2010-05-24 Created: 2010-05-24 Last updated: 2017-12-12Bibliographically approved
2. Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women
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, 684-690 p.Article 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
Keyword
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: 2017-12-08Bibliographically approved
3. Decreased TLR4 and Increased MIF Adipose Gene Expression Following Long-Term Diet Intervention
Open this publication in new window or tab >>Decreased TLR4 and Increased MIF Adipose Gene Expression Following Long-Term Diet Intervention
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-53465 (URN)
Available from: 2012-03-27 Created: 2012-03-27 Last updated: 2016-01-25

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