Leptin and the regulation of food intake, energy homeostasis and immunity with special focus on periparturient ruminants

Leptin and the regulation of food intake, energy homeostasis and immunity with special focus on periparturient ruminants
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DOI:
10.1016/s0739-7240(02)00119-4
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发表时间:
2001-11-01
影响因子:
2.1
通讯作者:
Boisclair, YR
Boisclair, YR
中科院分区:
农林科学2区
文献类型:
--
作者:
Ingvartsen, KL;Boisclair, YR

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瘦素的生物学在啮齿动物和人类中得到了最广泛的研究。瘦素参与调节食物摄入、能量稳态和免疫。瘦素主要在白色脂肪组织中产生,并通过膜结合受体家族起作用,包括具有长胞内结构域的同种型(OB-Rb)和具有短胞内结构域的许多同种型(Ob-Rs)。OB-Rb主要表达于参与食物摄入和能量稳态调节的下丘脑区域,其他亚型广泛分布,并且在大多数外周组织中以远高于OB-Rb的丰度发现。瘦素对食物摄入和能量稳态的作用是中心的,并且通过食欲神经肽(神经肽Y、甘丙肽、甘丙肽样肽、黑色素浓缩激素、食欲素、刺豚鼠相关肽)和食欲神经肽(促肾上腺皮质激素释放激素、阿黑皮素原、α-黑素细胞刺激激素以及可卡因和安非他明调节的转录物)的网络介导。此外,瘦素直接作用于免疫细胞以刺激造血、T细胞免疫、吞噬作用、细胞因子产生,并减弱对感染性损伤的易感性。反刍动物中的新数据表明,瘦素受许多因素和生理状态的动态调节。因此,瘦素是以脉动的方式分泌的,但没有明显的昼夜节律。生长期和泌乳期反刍动物的肥胖与血浆瘦素浓度呈正相关。妊娠期血浆瘦素浓度升高,分娩前1-2周开始下降,泌乳早期达到最低点。分娩时血浆瘦素的减少可能促进能量缺乏时期所需的中枢介导的适应,但可能对免疫细胞功能产生负面影响。未来的研究需要在反刍动物中解决瘦素和中枢神经系统在围产期和传染病期间协调代谢中所起的作用。(C)2002年爱思唯尔科技有限公司All rights reserved.
The biology of leptin has been studied most extensively in rodents and in humans. Leptin is involved in the regulation of food intake, energy homeostasis and immunity. Leptin is primarily produced in white adipose tissue and acts via a family of membrane bound receptors, including an isoform with a long intracellular domain (OB-Rb), and many isoforms with short intracellular domains (Ob-Rs). OB-Rb is predominantly expressed in the hypothalamic regions involved in the regulation of food intake and energy homeostasis, The other isoforms are distributed ubiquitously and are found in most peripheral tissues in far greater abundance than OB-Rb. The effects of leptin on food intake and energy homeostasis are central and are mediated via a network of orexigenic neuropeptides (neuropeptide Y, galanin, galanin-like peptide, melanin-concentrating hormone, orexins, agouti-related peptide) and anorexigenic neuropeptides (corticotropin-releasing hormone, pro-opiomelanocortin, alpha-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript). In addition, leptin acts directly on immune cells to stimulate hematopoesis, T-cell immunity, phagocytosis, cytokine production, and to attenuate susceptibility to infectious insults. Emerging data in ruminants suggest that leptin is dynamically regulated by many factors and physiological states. Thus, leptin is secreted in a pulsatile fashion, but without a marked diurnal rhythm. A positive relationship between adiposity and plasma leptin concentration exists in growing and lactating ruminants. The concentration of plasma leptin increases during pregnancy, starts to decline 1-2 wk before parturition, and reaches a nadir in early lactation. The reduction of plasma leptin at parturition is likely to promote centrally mediated adaptations required in periods of energy deficit, but could have negative effects on immune cell function. Future research is needed in ruminants to address the roles played by leptin and the central nervous system in orchestrating metabolism during the periparturient period and during infectious diseases. (C) 2002 Elsevier Science Inc. All rights reserved.