The taste receptor type I (Tas1R) family consists of three G protein-coupled receptors (T1R1, T1R2, and T1R3) that form heterodimers recognizing sweet compounds (T1R2/T1R3) or amino acids (T1R1/T1R3). These receptors are nutrient sensors that facilitate appropriate physiological responses with nutrient availability. However, their contribution to the development of pathologies associated with overnutrition (e.g., atherosclerosis) is unclear. The aim of the present study was to determine if T1R3 deletion would reduce atherosclerotic plaque development in mice. We generated atherosclerotic mice with whole-body deletion of T1R3 by crossing T1R3^−/− mice with ApoE^−/− mice. T1R3^+/+ ApoE^−/− and T1R3^−/− ApoE^−/− mice were maintained on an atherogenic high-fat diet for 8 weeks. Weight gain and food consumption were measured during the 8-week diet. Atherosclerotic lesion development and size were assessed by en face analysis of intact aortas and microscopic analysis of aortic roots. Our results indicate that T1R3 deletion in male and female ApoE^−/− mice reduces aortic atherosclerotic plaque accumulation. Hepatic triglyceride accumulation, which was measured by quantification of oil red O staining, was also reduced in T1R3^−/− mice. While the ablation of T1R3 reduced the final body weight of both males and females by approximately 12%, serum lipids, insulin, and glucose were either unchanged or slightly reduced. Immunoblot analysis of the phosphorylation of p70S6K, an effector of mTORC1, suggests T1R3 ablation reduces mTORC1 activity by approximately 50% in the male livers. Collectively, these findings suggest that the whole-body deletion of T1R3 reduces atherosclerosis and hepatic steatosis in a manner largely independent of the measured effects on whole-body glucose and lipid homeostasis.

I型味觉受体（Tas1R）家族由三个G蛋白偶联受体（T1R1，T1R2和T1R3）组成，它们形成识别甜味化合物（T1R2 / T1R3）或氨基酸（T1R1 / T1R3）的异二聚体。这些受体是营养素传感器，可促进营养素可利用的适当生理反应。但是，它们对与营养过剩相关的病理学发展（例如动脉粥样硬化）的贡献尚不清楚。本研究的目的是确定T1R3缺失是否会减少小鼠的动脉粥样硬化斑块的形成。我们通过将T1R3 ^-/-小鼠与ApoE ^-/-小鼠杂交，产生了全身缺失T1R3的动脉粥样硬化小鼠。T1R3 ^{+ / +} ApoE ^-/-和T1R3 ^-/- ApoE^-/-小鼠维持致动脉粥样硬化的高脂饮食8周。在8周的饮食中测量体重增加和食物消耗。动脉粥样硬化病变的发展和大小通过完整主动脉的面部分析和主动脉根的显微镜分析进行评估。我们的结果表明，雄性和雌性ApoE ^-/-小鼠中的T1R3缺失减少了主动脉粥样硬化斑块的积累。通过油红O染色的定量测得的肝甘油三酸酯积累在T1R3 ^-/-中也减少了老鼠。T1R3的消融使雄性和雌性的最终体重均降低了约12％，而血脂，胰岛素和葡萄糖则未改变或略有降低。对mTORC1的效应子p70S6K磷酸化的免疫印迹分析表明，T1R3消融可在男性肝脏中将mTORC1活性降低约50％。总而言之，这些发现表明，T1R3的全身缺失以很大程度上独立于对全身葡萄糖和脂质体内稳态的测定影响的方式减少了动脉粥样硬化和肝脂肪变性。