Macrophages and Adipocytes in Human Obesity

Capel, Frédéric; Klimčáková, Eva; Viguerie, Nathalie; Roussel, Bruno; Vítková, Michaela; Kováčiková, Michaela; Polàk, Jan; Kováčová, Zuzana; Galitzky, Jean; Maoret, Jean‐José; Hanacek, Jiri; Pers, Tune H.; Bouloumié, Anne; Štich, Vladimír; Langin, Dominique

doi:10.2337/db09-0033

Cited by 155 publications

(149 citation statements)

References 45 publications

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“…In line, our previous study showed a downregulation of both pro-inflammatory (for example, human leukocyte antigen-D region, osteopontin) and antiinflammatory (for example, interleukin-10) genes. 33 These findings favor 'the balanced macrophage activation hypothesis' that explains macrophage activation as a complex of cyclic processes to keep balance between pro-and Human adipose tissue macrophages during diet M Kováčiková et al anti-inflammatory states in inflamed tissue. 49 In the mouse, high-fat diet induces a recruitment of ATM with M1 properties and no change in M2 macrophages.…”

Section: Discussionmentioning

confidence: 97%

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Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

et al. 2010

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Objective: Accumulation of adipose tissue macrophages (ATMs) is observed in obesity and may participate in the development of insulin resistance and obesity-related complications. The aim of our study was to investigate the effect of long-term dietary intervention on ATM content in human adipose tissue. Design: We performed a multi-phase longitudinal study. Subjects and measurements: A total of 27 obese pre-menopausal women (age 39±2 years, body mass index 33.7±0.5 kg m -2 ) underwent a 6-month dietary intervention consisting of two periods: 4 weeks of very low-calorie diet (VLCD) followed by weight stabilization composed of 2 months of low-calorie diet and 3to 4 months of weight maintenance diet. At baseline and at the end of each dietary period, samples of subcutaneous adipose tissue (SAT) were obtained by needle biopsy and blood samples were drawn. ATMs were determined by flow cytometry using combinations of cell surface markers. Selected cytokine and chemokine plasma levels were measured using enzyme-linked immunosorbent assay. In addition, in a subgroup of 16 subjects, gene expression profiling of macrophage markers in SAT was performed using real-time PCR. Results: Dietary intervention led to a significant decrease in body weight, plasma insulin and C-reactive protein levels. After VLCD, ATM content defined by CD45 þ /14 þ /206 þ did not change, whereas it decreased at the end of the intervention. This decrease was associated with a downregulation of macrophage marker mRNA levels (CD14, CD163, CD68 and LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1)) and plasma levels of monocyte-chemoattractant protein-1 (MCP-1) and CXCL5 (chemokine (C-X-C motif) ligand 5). During the whole dietary intervention, the proportion of two ATM subpopulations distinguished by the CD16 marker was not changed. Conclusion: A 6-month weight-reducing dietary intervention, but not VLCD, promotes a decrease in the number of the whole ATM population with no change in the relative distribution of ATM subsets.

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Section: Discussionmentioning

confidence: 97%

“…33 Indeed, in the VLCD phase, there was an increase or no change in inflammation-and macrophagerelated genes. At the end of the whole dietary program, there was a coordinated downregulation of these genes including CD14, CD68 and CD163, as shown in this study.…”

Section: Discussionmentioning

confidence: 99%

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

et al. 2010

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“…13,48 In addition to cachexia, feeding a low-calorie diet has very recently been found in microarray studies to lead to a modest increase ZAG and adiposity C Bing et al in ZAG mRNA level in subcutaneous adipose tissue of obese women. 49 ZAG is also implicated in the development of adipose tissue by our recent study in rats during the first month after birth, in which ZAG protein levels were reduced at weaning when there is a large increase in fat mass. 50 A downregulation of ZAG expression in obesity has recently been reported in mice as well as in humans.…”

Section: Zag Expression and Body Fat Massmentioning

confidence: 91%

Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

et al. 2010

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The importance of white adipose tissue in the control of energy balance is now firmly recognized. In addition to fuel storage, adipocytes secrete an array of proteins factors (adipokines), which regulate multiple physiological and metabolic processes as well as influence body fat accumulation. Zinc-a2-glycoprotein (ZAG), a lipid mobilizing factor initially characterized as a tumor product associated with cachexia, has recently been identified as a novel adipokine. Although the exact role of ZAG in adipose tissue remains to be clarified, there is evidence that ZAG expression appears to be inversely related to adiposity, being upregulated in cachexia whereas reduced in obesity. Investigations on the regulation of ZAG give insights into its potential function in adipose tissue with a link to lipid mobilization and an anti-inflammatory action. Recent work shows that ZAG stimulates adiponectin secretion by human adipocytes. Data from genetic studies suggest that ZAG may be a candidate gene for body weight regulation; this is supported by the demonstration that ZAG-knockout mice are susceptible to weight gain, whereas transgenic mice overexpressing ZAG exhibit weight loss. The present review summarizes these new perspectives of ZAG and the potential mechanisms by which it might modulate adipose tissue mass and function.

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“…RNA analysis Total RNA isolation was performed as previously described [32]. The mRNA expression of macrophage-specific genes was assessed by reverse transcription and real-time quantitative PCR using a sequence detection system (ABI PRISM 7900; Applied Biosystems, Foster City, CA, USA) and custom TaqMan low-density arrays and TaqMan gene expression assay pre-loaded targets (both from Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat

et al. 2011

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Aims/hypothesis Our goal was to identify a set of human adipose tissue macrophage (ATM)-specific markers and investigate whether their gene expression in subcutaneous adipose tissue (SAT) as well as in visceral adipose tissue (VAT) is related to obesity and to the occurrence of the metabolic syndrome. Methods ATM-specific markers were identified by DNA microarray analysis of adipose tissue cell types isolated from SAT of lean and obese individuals. We then analysed gene expression of these markers by reverse transcription quantitative PCR in paired samples of SAT and VAT from 53 women stratified into four groups (lean, overweight, obese and obese with the metabolic syndrome). Anthropometric measurements, euglycaemic-hyperinsulinaemic clamp, blood analysis and computed tomography scans were performed. Results A panel of 24 genes was selected as ATM-specific markers based on overexpression in ATM compared with other adipose tissue cell types. In SAT and VAT, gene expression of ATM markers was lowest in lean and highest in the metabolic syndrome group. mRNA levels in the two fat depots were negatively correlated with glucose disposal rate and positively associated with indices of adiposity and the metabolic syndrome. Conclusions/interpretation In humans, expression of ATMspecific genes increases with the degree of adiposity and correlates with markers of insulin resistance and the metabolic syndrome to a similar degree in SAT and in VAT.

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Macrophages and Adipocytes in Human Obesity

Cited by 155 publications

References 45 publications

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat

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