MTCH2 in Human White Adipose Tissue and Obesity

Abstract

Genome-wide association studies have identified single-nucleotide polymorphisms in approximately 40 loci associated with obesity-related traits. How these loci regulate obesity is largely unknown. One obesity-associated single-nucleotide polymorphism is close to the MTCH2 gene (mitochondrial carrier homolog 2). The objective of the study was to assess the expression of genes in obesity-associated loci in abdominal sc white adipose tissue (scWAT) in relation to obesity. A more comprehensive expression study was performed on MTCH2. mRNA levels of 66 genes from 40 loci were determined by microarray in scWAT from lean and obese women (n = 30). MTCH2 mRNA was measured by quantitative RT-PCR in lean and obese before and after weight loss in intact adipose pieces and isolated adipocytes, paired samples of scWAT and omental WAT, and primary adipocyte cultures (n = 191 subjects in total). MTCH2 genotypes were compared with mRNA expression in 96 women. MTCH2 protein was examined in scWAT of 38 individuals. Adipose expression of eight genes was significantly associated with obesity; of these, MTCH2 displayed the highest absolute signal. MTCH2 mRNA and protein expression was significantly increased in obese women but was not affected by weight loss. MTCH2 was enriched in isolated fat cells and increased during adipocyte differentiation. There was no cis influence of MTCH2 genotypes on mRNA levels. MTCH2 is highly expressed in human WAT and adipocytes with increased levels in obese women. These results suggest that MTCH2 may play a role in cellular processes underlying obesity.