The MRC1/CD68 ratio is positively associated with adipose tissue lipogenesis and with muscle mitochondrial gene expression in humans

PLoS One. 2013 Aug 12;8(8):e70810. doi: 10.1371/journal.pone.0070810. eCollection 2013.

Abstract

Background: 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).

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adiponectin / genetics
  • Adiponectin / metabolism
  • Adipose Tissue / metabolism*
  • Adult
  • Antigens, CD / genetics*
  • Antigens, Differentiation, Myelomonocytic / genetics*
  • Female
  • Gene Expression Regulation*
  • Genes, Mitochondrial*
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Lipogenesis / genetics*
  • Male
  • Mannose Receptor
  • Mannose-Binding Lectins / genetics
  • Mannose-Binding Lectins / metabolism
  • Membrane Glycoproteins
  • Middle Aged
  • Mitochondria, Muscle / genetics*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Immunologic / genetics*
  • Subcutaneous Fat / metabolism
  • Transcriptome
  • Weight Loss / genetics

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Lectins, C-Type
  • MRC1 protein, human
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, Immunologic

Grants and funding

This work was supported by grant SAF-2009-10461 and grant PI11-00214 from the Ministerio de Economía y Competitividad, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.