Epi)genetic regulation of CRTC1 in human eating behaviour and fat distribution

Abstract Background In brain, CREB-regulated transcription co-activator 1 (CRTC1) is involved in metabolic dysregulation. In humans a SNP in CRTC1 was associated to body fat percentage and two SNPs affected RNA Pol II binding and chromatin structure, implying epigenetic regulation of CRTC1 . We sought to understand the relevance of CRTC1 SNPs, DNA methylation and expression in human eating behaviour and its relationship to clinical variables of obesity in blood and adipose tissue. Methods 13 CRTC1 SNPs were included to analyze eating behaviour. For rs7256986, follow up association analyses were applied on DNA methylation, CRTC1 expression and clinical parameters. Linear regression was used throughout the study adjusted for age, sex and BMI. Besides data extraction from previous work, rs7256986 was de-novo genotyped and DNA methylation was evaluated by using pyrosequencing. Findings We found several SNPs in the CRTC1 locus nominally associated with human eating behaviour or 2hr postprandial insulin levels and observed a correlation with alcohol and coffee intake (all P CRTC1 gene expression which in turn, related to BMI and fat distribution. Interpretation Our data support the known role of CRCT1 regulating energy metabolism in brain. Here, we highlight relevance of CRTC1 regulation in blood and adipose tissue. Fund IFB AdiposityDiseases (BMBF); n609020-Scientia Fellows; Helse-SorOst; DFG: CRC 1052/1 and/2; Kompetenznetz Adipositas, German Diabetes Association.