The MRC1/CD68 Ratio Is Positively Associated with Adipose Tissue Lipogenesis and with Muscle Mitochondrial Gene Expression in Humans

• Published in: PloS one Vol. 8; no. 8; p. e70810
• Main Authors: Moreno-Navarrete, José María, Ortega, Francisco, Gómez-Serrano, María, García-Santos, Eva, Ricart, Wifredo, Tinahones, Francisco, Mingrone, Geltrude, Peral, Belén, Fernández-Real, José Manuel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.08.2013; Public Library of Science (PLoS)
• Subjects: Adipocytes - metabolism; Adiponectin - genetics; Adiponectin - metabolism; Adipose tissue; Adipose Tissue - metabolism; Adult; Antigens, CD - genetics; Antigens, Differentiation, Myelomonocytic - genetics; Bariatric surgery; Biology; Body fat; Body mass; Body weight loss; Female; Gastrointestinal surgery; Gene expression; Gene Expression Regulation; Genes; Genes, Mitochondrial; Glucose; Humans; Immunohistochemistry; Inflammation; Insulin resistance; Kinases; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Lipogenesis; Lipogenesis - genetics; Macrophages; Male; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - metabolism; Medicine; Middle Aged; Mitochondria; Mitochondria, Muscle - genetics; Muscles; Obesity; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Immunologic - genetics; Rodents; Subcutaneous Fat - metabolism; Surgery; Transcriptome; Type 2 diabetes; Weight loss; Weight Loss - genetics; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0070810

Alternative macrophages (M2) express the cluster differentiation (CD) 206 (MCR1) at high levels. Decreased M2 in adipose tissue is known to be associated with obesity and inflammation-related metabolic disturbances. Here we aimed to investigate MCR1 relative to CD68 (total macrophages) gene expression in association with adipogenic and mitochondrial genes, which were measured in human visceral [VWAT, n = 147] and subcutaneous adipose tissue [SWAT, n = 76] and in rectus abdominis muscle (n = 23). The effects of surgery-induced weight loss were also longitudinally evaluated (n = 6). MCR1 and CD68 gene expression levels were similar in VWAT and SWAT. A higher proportion of CD206 relative to total CD68 was present in subjects with less body fat and lower fasting glucose concentrations. The ratio MCR1/CD68was positively associated with IRS1gene expression and with the expression of lipogenic genes such as ACACA, FASN and THRSP, even after adjusting for BMI. The ratio MCR1/CD68 in SWAT increased significantly after the surgery-induced weight loss (+44.7%; p = 0.005) in parallel to the expression of adipogenic genes. In addition, SWAT MCR1/CD68ratio was significantly associated with muscle mitochondrial gene expression (PPARGC1A, TFAM and MT-CO3). AT CD206 was confirmed by immunohistochemistry to be specific of macrophages, especially abundant in crown-like structures. A decreased ratio MCR1/CD68 is linked to adipose tissue and muscle mitochondrial dysfunction at least at the level of expression of adipogenic and mitochondrial genes.