Macrophages and Adipocytes in Human Obesity

Abstract

OBJECTIVEWe investigated the regulation of adipose tissue gene expression during different phases of a dietary weight loss program and its relation with insulin sensitivity.RESEARCH DESIGN AND METHODSTwenty-two obese women followed a dietary intervention program composed of an energy restriction phase with a 4-week very-low-calorie diet and a weight stabilization period composed of a 2-month low-calorie diet followed by 3–4 months of a weight maintenance diet. At each time point, a euglycemic-hyperinsulinemic clamp and subcutaneous adipose tissue biopsies were performed. Adipose tissue gene expression profiling was performed using a DNA microarray in a subgroup of eight women. RT–quantitative PCR was used for determination of mRNA levels of 31 adipose tissue macrophage markers (n = 22).RESULTSBody weight, fat mass, and C-reactive protein level decreased and glucose disposal rate increased during the dietary intervention program. Transcriptome profiling revealed two main patterns of variations. The first involved 464 mostly adipocyte genes involved in metabolism that were downregulated during energy restriction, upregulated during weight stabilization, and unchanged during the dietary intervention. The second comprised 511 mainly macrophage genes involved in inflammatory pathways that were not changed or upregulated during energy restriction and downregulated during weight stabilization and dietary intervention. Accordingly, macrophage markers were upregulated during energy restriction and downregulated during weight stabilization and dietary intervention. The increase in glucose disposal rates in each dietary phase was associated with variation in expression of sets of 80–110 genes that differed among energy restriction, weight stabilization, and dietary intervention.CONCLUSIONSAdipose tissue macrophages and adipocytes show distinct patterns of gene regulation and association with insulin sensitivity during the various phases of a dietary weight loss program.

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

“…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.…”

“…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.…”

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

“…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.…”

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

“…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).…”