Zhang Shan, Chen Jianhui, Li Qingqing, Zeng Wenwen
Institute for Immunology, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing 100084, China.
Life Metab. 2023 May 4;2(3):load018. doi: 10.1093/lifemeta/load018. eCollection 2023 Jun.
The thermogenic brown and beige adipocytes consume fatty acids and generate heat to maintain core body temperature in the face of cold challenges. Since their validated presence in humans, the activation of thermogenic fat has been an attractive target for treating obesity and related metabolic diseases. Here, we reported that the opioid growth factor receptor () was highly expressed in adipocytes and promoted thermogenesis. The mice with genetic deletion of in adipocytes displayed an impaired capacity to counter environmental cold challenges. Meanwhile, ablation in adipocytes led to reduced fatty acid oxidation, enhanced lipid accumulation, impaired glucose tolerance, and exacerbated tissue inflammation under chronic high-fat diet (HFD)-fed conditions. At the cellular level, OGFr enhanced the production of mitochondrial trifunctional protein subunit α (MTPα) and also interacted with MTPα, thus promoting fatty acid oxidation. Together, our study demonstrated the important role of OGFr in fatty acid metabolism and adipose thermogenesis.
产热的棕色和米色脂肪细胞消耗脂肪酸并产生热量，以在面临寒冷挑战时维持核心体温。自它们在人类中被证实存在以来，激活产热脂肪一直是治疗肥胖症及相关代谢疾病的一个有吸引力的靶点。在此，我们报道阿片样生长因子受体（OGFr）在脂肪细胞中高度表达并促进产热。脂肪细胞中基因缺失OGFr的小鼠应对环境寒冷挑战的能力受损。同时，在慢性高脂饮食（HFD）喂养条件下，脂肪细胞中OGFr缺失导致脂肪酸氧化减少、脂质积累增加、葡萄糖耐量受损以及组织炎症加剧。在细胞水平上，OGFr增强了线粒体三功能蛋白亚基α（MTPα）的产生，并且还与MTPα相互作用，从而促进脂肪酸氧化。总之，我们的研究证明了OGFr在脂肪酸代谢和脂肪产热中的重要作用。
