Ablation of Tas1r1 Reduces Lipid Accumulation Through Reducing the de Novo Lipid Synthesis and Improving Lipid Catabolism in Mice.

Abstract

Amino acid sensing plays an important role in regulating lipid metabolism by sensing amino acid nutrient disturbance. T1R1 (umami taste receptor, type 1, member 1) is a membrane G protein-coupled receptor that senses amino acids. Tas1r1-knockout (KO) mice were used to explore the function of umami receptors in lipid metabolism. Compared with wild-type (WT) mice, Tas1r1-KO mice showed decreased fat mass (P < 0.05) and adipocyte size, lower liver triglyceride (7.835 ± 0.809 vs 12.463 ± 0.916 mg/g WT, P = 0.013) and total cholesterol levels (0.542 ± 0.109 vs 1.472 ± 0.044 mmol/g WT, P < 0.001), and reduced lipogenesis gene expressions in adipose and liver tissues. Targeted liver amino acid metabolomics showed that the amino acid content of Tas1r1-KO mice was significantly decreased, which was consistent with the branched-chain ketoacid dehydrogenase protein levels. Proteomics analysis showed that the upregulated proteins were enriched in lipid and steroid metabolism pathways, and parallel reaction monitoring results illustrated that Tas1r1 ablation promoted lipid catabolism through oxysterol 7 α-hydroxylase and insulin-like growth factor binding protein 2. In summary, Tas1r1 disruption in mice could reduce lipid accumulation by reducing de novo lipid synthesis and improving lipid catabolism.