Adipose tissue macrophages inhibit adipogenesis of mesenchymal precursor cells via wnt-5a in humans

• Published in: International Journal of Obesity 2011-11, Vol.35 (11), p.1450-1454
• Main Authors: Bilkovski, R, Schulte, D.M, Oberhauser, F, Mauer, J, Hampel, B, Gutschow, C, Krone, W, Laudes, M
• Format: Article
• Language: English
• Subjects: 631/250/2504/342; 631/80/86; 692/699/2743/137/773; 692/699/2743/393; Adipocytes; Adipocytes - metabolism; Adipocytes - pathology; Adipogenesis; Adipose tissue; Adipose Tissue - pathology; Adipose tissues; antibodies; Biological and medical sciences; Biopsy; Blood; Body fat; Cell culture; Cells, Cultured; Cytokines; Development and progression; Diabetes; Epidemiology; Female; Health Promotion and Disease Prevention; Human subjects; Humans; Immunohistochemistry; Inflammation; Insulin resistance; Internal Medicine; Macrophages; Macrophages - metabolism; Male; Medical sciences; Medicine; Medicine & Public Health; Mesenchymal Stromal Cells - metabolism; Metabolic Diseases; Middle Aged; monocytes; neutralization; noninsulin-dependent diabetes mellitus; Obesity; Obesity - genetics; Obesity - metabolism; Obesity - pathology; patients; Physiological aspects; Proto-Oncogene Proteins - metabolism; Public Health; quantitative polymerase chain reaction; Risk factors; RNA; secretion; short-communication; Signal Transduction; Tumor necrosis factor-TNF; Wnt Proteins - metabolism; Wnt-5a Protein
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2011.6

In patients with obesity and type 2 diabetes, adipose tissue is infiltrated by macrophages known to alter adipogenesis of mesenchymal precursor cells via secretion of proinflammatory cytokines. Recently, it has been shown that under certain conditions, immune cells can also express wnt-5a, a factor known to inhibit adipogenesis in humans. Therefore, in this study we aimed to investigate whether macrophages affect adipogenesis of mesenchymal precursor cells via wnt-5a. Wnt-5a was found to be expressed in adipose tissue macrophages in obese and type 2 diabetic human subjects in vivo by immunohistochemistry of adipose tissue biopsies. Furthermore, wnt-5a was detectable in circulating CD14+ blood monocytes of human subjects with obesity and type 2 diabetes on RNA level by real-time PCR. Besides expression analysis in vivo, we also performed functional studies to explore the role of wnt-5a in low-grade inflammation of adipose tissue. In a cell culture experiment, macrophage-conditioned differentiation medium inhibited adipogenesis of 3T3-L1 cells. This inhibitory effect was restored by adding neutralising anti-wnt-5a antibodies. In conclusion, our data indicate that macrophages alter adipogenesis of 3T3-L1 cells not only via classical proinflammatory cytokines, but also via wnt signalling molecules.