Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institutes of Biomedical Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200438, China.
State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Sci China Life Sci. 2022 Nov;65(11):2287-2300. doi: 10.1007/s11427-022-2157-y. Epub 2022 Sep 23.
Brown adipose tissue (BAT) plays an essential role in non-shivering thermogenesis. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) is identified as a lipid transporter that reciprocally transfers phospholipids between intracellular membrane structures. However, the physiological significance of PITPNC1 and its regulatory mechanism remain unclear. Here, we demonstrate that PITPNC1 is a key player in thermogenesis of BAT. While Pitpnc1 mice do not differ with wildtype mice in body weight and insulin sensitivity on either chow or high-fat diet, they develop hypothermia when subjected to acute cold exposure at 4°C. The Pitpnc1 brown adipocytes exhibit defective β-oxidation and abnormal thermogenesis-related metabolism pathways in mitochondria. The deficiency of lipid mobilization in Pitpnc1 brown adipocytes might be the result of excessive accumulation of phosphatidylcholine and a reduction of phosphatidic acid. Our findings have uncovered significant roles of PITPNC1 in mitochondrial phospholipid homeostasis and BAT thermogenesis.
棕色脂肪组织（BAT）在非颤抖性产热中起着至关重要的作用。磷酸肌醇转移蛋白，细胞质 1（PITPNC1）被鉴定为一种脂质转运蛋白，可在细胞内膜结构之间反向转运磷脂。然而，PITPNC1 的生理意义及其调节机制尚不清楚。在这里，我们证明 PITPNC1 是 BAT 产热的关键因素。虽然 Pitpnc1 小鼠在普通饮食或高脂肪饮食下的体重和胰岛素敏感性与野生型小鼠没有差异，但它们在 4°C 的急性冷暴露下会出现体温过低。Pitpnc1 棕色脂肪细胞表现出β-氧化缺陷和线粒体中异常的产热相关代谢途径。Pitpnc1 棕色脂肪细胞中脂质动员的缺陷可能是由于磷脂酰胆碱过度积累和磷脂酸减少所致。我们的研究结果揭示了 PITPNC1 在线粒体磷脂稳态和 BAT 产热中的重要作用。
