Feng Yue-Yao, Zhang Yu-Jie, Chang Yong-Sheng
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China.
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Sheng Li Xue Bao. 2021 Oct 25;73(5):821-827.
β3-adrenergic agonists induce adaptive thermogenesis and promote beiging of white fat. However, it remains unclear which metabolites mediate the stimulatory effects of β3-adrenergic agonists on thermogenesis of brown and beige fat. In this study, adipose tissue was isolated from 8-week-old C57/BL6J male mice by intraperitoneal administration of β3-adrenergic agonist CL316,243 for RNA-Seq, which revealed that histidine decarboxylase, a key enzyme in histamine synthesis, was strongly induced in adipose by CL316,243. Therefore, we speculated that histamine might be involved in the process of thermogenesis in adipose tissue. We determined the physiological role and mechanism by which histamine promotes fat thermogenesis by intravenous administering histamine to C57BL/6J mice fed a normal or a high-fat diet. The results showed that intravenous injection of histamine into C57BL/6J mice fed a normal diet stimulated the expression of thermogenic genes, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein 1 (UCP1), in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT). H&E staining also suggested that histamine treatment decreased the size of lipid droplets in adipocytes. Moreover, histamine treatment also enhanced thermogenesis of fat in high-fat diet induced obese mice, and improved glucose intolerance and fatty liver phenotype. Finally, we demonstrated that the effects of histamine on the thermogenic program were cell autonomous. Our data suggest that histamine may mediate the effects of β3-adrenergic agonists on thermogenesis of fat.
β3 肾上腺素能激动剂可诱导适应性产热并促进白色脂肪棕色化。然而，尚不清楚哪些代谢产物介导β3 肾上腺素能激动剂对棕色和米色脂肪产热的刺激作用。在本研究中，通过腹腔注射β3 肾上腺素能激动剂 CL316,243 从 8 周龄的 C57/BL6J 雄性小鼠中分离脂肪组织用于 RNA 测序，结果显示组胺合成中的关键酶组氨酸脱羧酶在脂肪组织中被 CL316,243 强烈诱导。因此，我们推测组胺可能参与脂肪组织的产热过程。我们通过向喂食正常或高脂饮食的 C57BL/6J 小鼠静脉注射组胺来确定组胺促进脂肪产热的生理作用和机制。结果表明，向喂食正常饮食的 C57BL/6J 小鼠静脉注射组胺可刺激棕色脂肪组织（BAT）和腹股沟白色脂肪组织（iWAT）中产热基因的表达，包括过氧化物酶体增殖物激活受体γ 共激活因子-1α（PGC-1α）和解偶联蛋白 1（UCP1）。苏木精-伊红染色也表明组胺处理可减小脂肪细胞中脂滴的大小。此外，组胺处理还增强了高脂饮食诱导的肥胖小鼠的脂肪产热，并改善了葡萄糖不耐受和脂肪肝表型。最后，我们证明组胺对产热程序的影响是细胞自主性的。我们的数据表明组胺可能介导β3 肾上腺素能激动剂对脂肪产热的作用。
