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


CONCLUSIONS
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.
Service of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
José María
JM
Moreno-Navarrete
Francisco
F
Ortega
María
M
Gómez-Serrano
Eva
E
García-Santos
Wifredo
W
Ricart
Francisco
F
Tinahones
Geltrude
G
Mingrone
Belén
B
Peral
José Manuel
JM
Fernández-Real
D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D050155:Lipogenesis / Q000235:genetics*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics*; D050151:Subcutaneous Fat / Q000378:metabolism; D059467:Transcriptome; D015431:Weight Loss / Q000235:genetics; D000097382:CD68 Molecule
D052242:Adiponectin; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C499918:ADIPOQ protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C573543:MRC1 protein, human