Macrophage Infiltration into Omental<i>Versus</i>Subcutaneous Fat across Different Populations: Effect of Regional Adiposity and the Comorbidities of Obesity

Harman-Boehm, Ilana; Blüher, Matthias; Redel, Henry; Sion-Vardy, Netta; Ovadia, Shira; Avinoach, Eliezer; Shai, Iris; Klöting, Nora; Stümvoll, Michael; Bashan, Nava; Rudich, Assaf

doi:10.1210/jc.2006-1811

Cited by 505 publications

(406 citation statements)

References 19 publications

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“…5,6 Obesity-associated adipose tissue inflammation is characterized by an increased abundance of adipose tissue macrophages in mice; 6,7 several studies have confirmed a correlation between body mass index (BMI) and adipose tissue macrophage numbers in humans particularly in the metabolically relevant visceral adipose tissue. [8][9][10][11] Therefore, adipose tissue macrophages are assumed to critically contribute to the pathogenesis of type 2 diabetes mellitus and the metabolic syndrome by driving obesity-associated chronic inflammation. In contrast, adipose tissue macrophages may also have cytoprotective anti-inflammatory properties, as identified by the expression of several markers that determine an alternatively activated, anti-inflammatory macrophage type, 12,13 for instance, the hemoglobin scavenger receptor CD163.…”

Section: Introductionmentioning

confidence: 99%

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

et al. 2009

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Objective: Insulin resistance in visceral obesity is substantially driven by adipose tissue inflammation, particularly by macrophages accumulating in obese adipose tissue. In contrast, adipose tissue macrophages express the hemoglobin scavenger receptor (CD163) and heme oxygenase-1 (gene: HMOX1) that together protect from oxidative stress. Our aim was to evaluate the expression of CD163 and HMOX1 in intra-abdominal visceral (omental) and subcutaneous adipose tissue as well as circulating soluble CD163 concentrations in human obesity and its association with adipose tissue inflammation, body fat distribution and insulin resistance. Methods: CD163, HMOX1 and CD68 mRNA expression in visceral and subcutaneous adipose tissue, serum concentration of soluble CD163 in morbidly obese patients (body mass index (BMI) 440 kg m À2 ), who underwent laparoscopic surgery for gastric banding (n ¼ 20), matched for age and sex to controls (BMIo30 kg m À2 ; n ¼ 20) was analyzed. Results: CD163 expression was highly upregulated in human adipose tissue and soluble CD163 serum concentration was elevated in obese vs lean subjects. HMOX1 was upregulated in adipose tissue by obesity as well and expressed predominantly in macrophages. Although CD163 expression strictly correlated with macrophage abundance, HMOX1 was additionally upregulated within macrophages. This upregulation was significantly lower in visceral compared with subcutaneous adipose tissue. Strikingly, relative visceral adipose tissue expression of HMOX1 negatively correlated with waist-to-hip ratio and the homeostasis model assessment of insulin resistance (both P ¼ 0.024). Conclusions: Visceral obesity is associated with defective upregulation of heme oxygenase-1 in visceral adipose tissue. A lack of this antioxidative and anti-inflammatory enzyme in visceral adipose tissue could contribute to the development of insulin resistance.

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Section: Introductionmentioning

confidence: 99%

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

et al. 2009

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“…For example, macrophage infiltration is more important in omental fat than in subcutaneous fat and increases with BMI. 35,36 Considering the fact that macrophages could represent an important percentage of cells in obese men and women, this could contribute to the differential expression of genes implicated in adipogenesis or lipid metabolism. In the present study, however, women covered a wide range of BMI values, which should attenuate the possible contribution of macrophages in the expression profiles examined.…”

Section: Discussionmentioning

confidence: 99%

Hypertrophy and hyperplasia of abdominal adipose tissues in women

et al. 2007

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Objective: To examine the expression of selected transcription factors involved in adipogenesis and genes related to lipid metabolism in abdominal subcutaneous and omental fat tissue. Research design and methods: We obtained subcutaneous and omental adipose tissue samples from 40 women undergoing abdominal hysterectomies (age: 4775 years; BMI 27.975.3 kg/m 2 ). We measured isolated adipocyte size and metabolism, and detailed measures of body fat accumulation and body fat distribution were obtained (dual-energy X-ray absorptiometry and computed tomography, respectively). Results: Adipocyte size of both subcutaneous and omental fat were increased with higher body fat mass values, with similar regression slopes in each compartment. In contrast, with higher body fat mass values, fat accumulation was progressively higher in the subcutaneous than in the visceral fat compartment, suggesting hyperplasia in the subcutaneous fat compartment. Messenger RNA levels of CEBPa, PPARg2, SREBP1c and genes related to lipid metabolism (LPL, FABP4, DGAT1, DGAT2, PLIN and HSL) were significantly higher in subcutaneous than in omental fat tissue (Pp0.001 for all). Only subcutaneous expression of these genes tracked with obesity levels as reflected by significant positive associations between subcutaneous fat CEBPa, SREBP1c and DGAT2 expression and total body fat mass (r ¼ 0.37, r ¼ 0.41, r ¼ 0.57, respectively, Pp0,05), fat percentage (r ¼ 0.40, r ¼ 0.39, r ¼ 058, respectively, Pp0,05) and subcutaneous adipose tissue area (r ¼ 0.36, r ¼ 0.38, r ¼ 0.58, respectively, Pp0,05). Omental adipose tissue expression levels of these genes were not significantly related to adiposity measures. Conclusions: These results show that in obese women, hyperplasia is predominant in the subcutaneous fat depot, whereas fat cell hypertrophy is observed both in the omental and subcutaneous compartments.

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“…Paired human visceral (visc) and subcutaneous (sc) fat tissue samples were obtained from the Leipzig (Germany) cohort fat tissue bank described in previous studies (Harman-Boehm et al, 2007). A c c e p t e d M a n u s c r i p t 8…”

Section: Experimental Subjectsmentioning

confidence: 99%

An inflammatory micro-environment promotes human adipocyte apoptosis

Keuper

Blüher

Schön

et al. 2011

Molecular and Cellular Endocrinology

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Obesity-associated macrophage infiltration into adipose tissue is responsible for both local and systemic inflammation. Recent findings suggest fat cell apoptosis as an initiator of macrophage recruitment.Here, we investigated the effects of an inflammatory micro-environment on fat cells by using human THP-1 macrophages and SGBS adipocytes. Macrophage-secreted factors induced insulin resistance, inhibited insulin-stimulated Akt phosphorylation, and induced apoptosis of adipocytes. The apoptosisinducing effect was even more pronounced in direct co-cultures of adipocytes and macrophages. Our data suggest a link between insulin resistance and apoptosis sensitivity. Accordingly, pharmacological and genetic inhibition of insulin signaling at the level of Akt2 sensitized adipocytes to apoptosis induction by macrophage-secreted factors.In conclusion, we describe here a novel interaction of macrophages and fat cells, i.e. induction of apoptosis. Our data suggest a feed-forward cycle in which macrophages further drive the inflammatory process by inducing insulin resistance and concomitant apoptosis of adipocytes.

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Macrophage Infiltration into OmentalVersusSubcutaneous Fat across Different Populations: Effect of Regional Adiposity and the Comorbidities of Obesity

Abstract: Preferential macrophage infiltration into OM fat is a general phenomenon exaggerated by central obesity, potentially linking central adiposity with increased risk of diabetes and coronary heart disease.

Cited by 505 publications

References 19 publications

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

Hypertrophy and hyperplasia of abdominal adipose tissues in women

An inflammatory micro-environment promotes human adipocyte apoptosis

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