Wada Nobuhiro, Hirako Satoshi, Takenoya Fumiko, Kageyama Haruaki, Okabe Mai, Shioda Seiji
Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai Shinagawa-ku, Tokyo 142-8555, Japan.
Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai Shinagawa-ku, Tokyo 142-8555, Japan; Department of Physical Education, Hoshi University School of Pharmacy and Pharmaceutical Science, Tokyo 142-8501, Japan.
J Chem Neuroanat. 2014 Nov;61-62:191-9. doi: 10.1016/j.jchemneu.2014.09.002. Epub 2014 Sep 16.
Leptin is mainly produced in the white adipose tissue before being secreted into the blood and transported across the blood-brain barrier. Leptin binds to a specific receptor (LepR) that has numerous subtypes (LepRa, LepRb, LepRc, LepRd, LepRe, and LepRf). LepRb, in particular, is expressed in several brain nuclei, including the arcuate nucleus, the paraventricular nucleus, and the dorsomedial, lateral and ventromedial regions of the hypothalamus. LepRb is also co-expressed with several neuropeptides, including proopiomelanocortin, neuropeptide Y, galanin, galanin-like peptide, gonadotropin-releasing hormone, tyrosine hydroxylase and neuropeptide W. Functionally, LepRb induces activation of the JAK2/ERK, /STAT3, /STAT5 and IRS/PI3 kinase signaling cascades, which are important for the regulation of energy homeostasis and appetite in mammals. In this review, we discuss the structure, genetics and distribution of the leptin receptors, and their role in cell signaling mechanisms.
瘦素主要在白色脂肪组织中产生,然后分泌到血液中,并穿过血脑屏障进行运输。瘦素与一种具有多种亚型(LepRa、LepRb、LepRc、LepRd、LepRe和LepRf)的特异性受体(LepR)结合。特别是LepRb,在包括弓状核、室旁核以及下丘脑的背内侧、外侧和腹内侧区域在内的多个脑核中表达。LepRb还与几种神经肽共同表达,包括阿黑皮素原、神经肽Y、甘丙肽、甘丙肽样肽、促性腺激素释放激素、酪氨酸羟化酶和神经肽W。在功能上,LepRb诱导JAK2/ERK、/STAT3、/STAT5和IRS/PI3激酶信号级联的激活,这些信号级联对于调节哺乳动物的能量平衡和食欲很重要。在这篇综述中,我们讨论了瘦素受体的结构、遗传学和分布,以及它们在细胞信号传导机制中的作用。