TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population

Abstract The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause Non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidemia, etc. Systematic investigation of the key factors related to hepatic glucose metabolism may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. Here, we quantified oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes in BXD mice under chow and high-fat diet conditions. Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background. To further identify the candidate genes associated with hepatic glucose metabolism, and the results revealed 9 genetic regulating loci on chromosomes 1, 4, 7 and 11, respectively by QTL mapping. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate functional genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 significantly decreased the glucose uptake. RT-PCR assays confirmed that the down-regulation of those three candidates inhibited the transcription of genes related to insulin and glucose metabolism pathways. Consequently, our study uncovered the role of TEAD1, MYO7A and NDUFC2 that influenced the mitochondrial function in to regulate glucose homeostasis and provided novel targets for the diagnosis, treatment, and prognosis of glucose metabolism-related diseases.