Adipose tissue as an endocrine organ
Adipose tissue as an endocrine organ
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DOI：
10.1038/oby.2006.317
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发表时间：
2006-08-01
期刊：
影响因子：
6.9
通讯作者：
Ahima, Rexford S.
中科院分区：
文献类型：
--
作者：
Ahima, Rexford S.
脂肪组织在能量平衡中起关键作用，不仅储存甘油三酯，还对营养、神经和激素信号做出反应，并分泌控制摄食、产热、免疫和神经内分泌功能的脂肪因子。瘦素的增加通过下丘脑和脑干神经元的受体向大脑发出饱腹感的信号。瘦素激活酪氨酸激酶、Janus激酶2、信号转导和转录激活子3，导致厌食性多肽，如α-黑素细胞刺激素、可卡因和苯丙胺调节的转录本水平增加，并抑制增食性多肽，如神经肽Y和刺鼠相关肽。肥胖的特征是高瘦素血症和下丘脑瘦素抵抗，部分原因是细胞因子信号转导-3抑制因子的诱导。瘦素在禁食期间迅速下降，有力地刺激食欲，减少产热，并介导抑制甲状腺和生殖激素以及激活下丘脑-垂体-肾上腺轴。这些活动由丘脑下丘脑束旁核整合。瘦素还通过涉及AMP激活的蛋白激酶(AMPK)的中枢和外周途径降低血糖并刺激脂解。脂联素仅由脂肪细胞分泌，与血糖、血脂和心血管调节有关。肥胖、糖尿病和动脉粥样硬化与脂联素水平降低有关，而脂联素治疗部分通过激活肝脏和肌肉中的AMPK来逆转这些异常。脂联素在大脑中的应用重述了增加脂肪酸氧化的外周作用。和胰岛素敏感性，并降低血糖。尽管脂联素受体广泛存在于外周器官和脑中，但目前尚不确定脂联素是否只通过这些靶点起作用。与瘦素一样，脂联素需要中枢黑素皮质素途径。此外，脂联素至少部分地通过激活肌肉和肝脏中的AMPK来刺激脂肪酸氧化和降低血糖和血脂。
Adipose tissue plays a critical role in energy homeostasis, not only in storing triglycerides, but also responding to nutrient, neural, and hormonal signals and secreting adipokines that control feeding, thermogenesis, immunity, and neuroendocrine function. A rise in leptin signals satiety to the brain through receptors in hypothalamic and brainstem neurons. Leptin activates tyrosine kinase, Janus kinase 2, and signal transducer and activator of transcription 3, leading to increased levels of anorexigenic peptides, e.g., a-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript, and inhibition of orexigenic peptides, e.g., neuropeptide Y and agouti-related peptide. Obesity is characterized by hyperleptinemia and hypothalamic leptin resistance, partly caused by induction of sup-pressor of cytokine signaling-3. Leptin falls rapidly during fasting and potently stimulates appetite, reduces thermogenesis, and mediates the inhibition of thyroid and reproductive hormones and activation of the hypothalamic-pituitary-adrenal axis. These actions are integrated by the paraventicular hypothalamic nucleus. Leptin also decreases glucose and stimulates lipolysis through central and peripheral pathways involving AMP-activated protein kinase (AMPK). Adiponectin is secreted exclusively by adipocytes and has been linked to glucose, lipid, and cardiovascular regulation. Obesity, diabetes, and atherosclerosis have been associated with reduced adiponectin levels, whereas adiponectin treatment reverses these abnormalities partly through activation of AMPK in liver and muscle. Administration of adiponectin in the brain recapitulates the peripheral actions to increase fatty acid oxidation. and insulin sensitivity and reduce glucose. Although putative adiponectin receptors are widespread in peripheral organs and brain, it is uncertain whether adiponectin acts exclusively through these targets. As with leptin, adiponectin requires the central melanocortin pathway. Furthermore, adiponectin stimulates fatty acid oxidation and reduces glucose and lipids, at least in part, by activating AMPK in muscle and liver.