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

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. -knockout (KO) mice were used to explore the function of umami receptors in lipid metabolism. Compared with wild-type (WT) mice, -KO mice showed decreased fat mass ( < 0.05) and adipocyte size, lower liver triglyceride (7.835 ± 0.809 12.463 ± 0.916 mg/g WT, = 0.013) and total cholesterol levels (0.542 ± 0.109 1.472 ± 0.044 mmol/g WT, < 0.001), and reduced lipogenesis gene expressions in adipose and liver tissues. Targeted liver amino acid metabolomics showed that the amino acid content of -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 ablation promoted lipid catabolism through oxysterol 7 α-hydroxylase and insulin-like growth factor binding protein 2. In summary, disruption in mice could reduce lipid accumulation by reducing lipid synthesis and improving lipid catabolism.