Department of Diabetes, Metabolism and Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Adv Exp Med Biol. 2024;1461:161-175. doi: 10.1007/978-981-97-4584-5_11.
Brown and beige adipocytes produce heat from substrates such as fatty acids and glucose. Such heat productions occur in response to various stimuli and are called adaptive non-shivering thermogenesis. This review introduces mechanisms known to regulate brown and beige adipocyte thermogenesis. Leptin and fibroblast growth factor 21 (FGF21) are examples of periphery-derived humoral factors that act on the central nervous system (CNS) and increase brown adipose tissue (BAT) thermogenesis. Additionally, neuronal signals such as those induced by intestinal cholecystokinin and hepatic peroxisome proliferator-activated receptor γ travel through vagal afferent-CNS-sympathetic efferent-BAT pathways and increase BAT thermogenesis. By contrast, some periphery-derived humoral factors (ghrelin, adiponectin, plasminogen activator inhibitor-1, and soluble leptin receptor) act also on CNS but inhibit BAT thermogenesis. Neuronal signals also reduce BAT sympathetic activities and BAT thermogenesis, one such example being signals derived by hepatic glucokinase activation. Beige adipocytes can be induced by myokines (interleukin 6, irisin, and β-aminoisobutyric acid), hepatokines (FGF21), and cardiac-secreted factors (brain natriuretic peptide). Cold temperature and leptin also stimulate beige adipocytes via sympathetic activation. Further investigation on inter-organ communication involving adipocyte thermogenesis may lead to the elucidation of how body temperature is regulated and, moreover, to the development of novel strategies to treat metabolic disorders.
棕色和米色脂肪细胞可从脂肪酸和葡萄糖等底物产热。这种产热是对各种刺激的反应，被称为适应性非颤抖性产热。本综述介绍了已知调节棕色和米色脂肪细胞产热的机制。瘦素和成纤维细胞生长因子 21（FGF21）是外周源性体液因子的例子，它们作用于中枢神经系统（CNS）并增加棕色脂肪组织（BAT）的产热。此外，肠胆囊收缩素和肝过氧化物酶体增殖物激活受体γ诱导的神经元信号通过迷走传入-CNS-交感传出-BAT 途径传递，并增加 BAT 的产热。相比之下，一些外周源性体液因子（ghrelin、脂联素、纤溶酶原激活物抑制剂-1 和可溶性瘦素受体）也作用于 CNS，但抑制 BAT 产热。神经元信号还降低 BAT 的交感神经活动和 BAT 的产热，肝葡萄糖激酶激活产生的信号就是一个例子。米色脂肪细胞可由肌肉因子（白细胞介素 6、鸢尾素和β-氨基异丁酸）、肝因子（FGF21）和心脏分泌的因子（脑利钠肽）诱导。寒冷温度和瘦素也通过交感神经激活刺激米色脂肪细胞。进一步研究涉及脂肪细胞产热的器官间通讯，可能有助于阐明体温是如何调节的，而且还可能开发出治疗代谢紊乱的新策略。
