The Role of T1R3 Receptor Protein in Lipid Synthesis Regulation in the Liver during Energy Metabolism

Membrane receptors of the T1R (1–3) “taste” family not only mediate sweet and amino acid taste perception in vertebrates but also participate in the regulation of carbohydrate and lipid metabolism. These receptors, expressed outside the oral cavity, influence the secretion of metabolic hormones, intestinal sugar absorption, and tissue growth/survival; however, many of their effects remain poorly understood. Specifically, the influence of the T1R3 receptor on liver function and overall energy metabolism has been insufficiently characterized and therefore became the objective of the present work. The study was carried out on male mice of the two inbred mouse strains: control C57BL/6J strain carrying the dominant allele of the Tas1r3 gene, encoding the T1R3 receptor with high affinity for sweet substances, and C57BL/6J-Tas1r3 tm1Rfm, a knockout strain lacking the functional Tas1r3 gene. Using indirect calorimetry, it was shown for the first time that the Tas1r3 genotype influences overall energy metabolism. In the postprandial state, the presence of functionally active T1R3 protein promoted total energy expenditure, enhanced carbohydrate oxidation, reduced lipid oxidation, and increased locomotor activity. During fasting, T1R3 contributed to maintaining a higher level of total energy expenditure, stimulated lipid oxidation and locomotor activity. A stimulating effect of T1R3 on hepatic lipogenic activity was revealed, as its presence increased the levels of low- and high-density lipoproteins and total cholesterol. The protein influenced the expression of genes involved in lipid and glycogen metabolism in the liver. In the postprandial state, T1R3 promoted increased expression of the insulin receptor and hepatic lipase. During fasting, T1R3 stimulated the expression of glycogen phosphorylase and hepatic lipase, while suppressing the expression of glycogen synthase. Upon post-fasting glucose entry into the bloodstream, the protein facilitated its utilization for energy needs, limiting the replenishment of glycogen stores. At the same time, its own expression was suppressed. The obtained data provide new insights into the mechanisms underlying T1R3 influence on the regulation of energy metabolism.