The Ablation of T1R1 Reduces Lipid Accumulation Through Reducing the De Novo Lipid Synthesis and Improving Lipid Metabolism in Mice

Abstract

Background: That cells sense extracellular amino acids to regulate intracellular lipid metabolism has been a heated debate in terms of the study on amino acid nutrition. T1R1 is a membrane G protein-coupled receptor that senses amino acids in a variety of cells. In our study, T1R1-KO mice was used to explore the function of umami taste receptor in lipid metabolism. Results: Compared with wild-type mice, T1R1-KO mice showed Significantly lighter adipose tissue weight, reduced serum triglycerides (TG) and total cholesterol (TC), as well as higher glucose tolerance on chow diet. Moreover, there were less lipid accumulation in adipose and liver tissue and shrink of the adipocyte size in T1R1-KO mice. And a decreased expression of lipogenesis genes (PPARγ, CEBPα, SREBP1) was found in both adipose and liver tissue. To further study the mechanism of T1R1 regulating liver lipid metabolism, proteomics analysis was introduced and the up-regulated proteins were enriched in lipid and steroid metabolism pathways of T1R1-KO mice. Further PRM verification analysis showed that the ablation of T1R1 reduced the de novo synthesis of lipids through BCKDHA and BCKDHB, and promoted lipid metabolism through CYP7B1 and IGFBP2. Conclusions: Our results showed that the disruption of T1R1 in mice could reduce body lipid accumulation, and our data clarifies the role of umami receptors in lipid metabolism and could provide a basis for the research on nutrition and obesity.