Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.
Endocrinology. 2010 Jul;151(7):3169-80. doi: 10.1210/en.2009-1358. Epub 2010 Apr 28.
Nesfatin-1 is a recently identified anorexigenic peptide derived from its precursor protein, nonesterified fatty acid/nucleobindin 2 (NUCB2). Although the hypothalamus is pivotal for the maintenance of energy homeostasis, adipose tissue plays an important role in the integration of metabolic activity and energy balance by communicating with peripheral organs and the brain via adipokines. Currently no data exist on nesfatin-1 expression, regulation, and secretion in adipose tissue. We therefore investigated NUCB2/nesfatin-1 gene and protein expression in human and murine adipose tissue depots. Additionally, the effects of insulin, dexamethasone, and inflammatory cytokines and the impact of food deprivation and obesity on nesfatin-1 expression were studied by quantitative RT-PCR and Western blotting. We present data showing NUCB2 mRNA (P < 0.001), nesfatin-1 intracellular protein (P < 0.001), and secretion (P < 0.01) were significantly higher in sc adipose tissue compared with other depots. Also, nesfatin-1 protein expression was significantly increased in high-fat-fed mice (P < 0.01) and reduced under food deprivation (P < 0.01) compared with controls. Stimulation of sc adipose tissue explants with inflammatory cytokines (TNFalpha and IL-6), insulin, and dexamethasone resulted in a marked increase in intracellular nesfatin-1 levels. Furthermore, we present evidence that the secretion of nesfatin-1 into the culture media was dramatically increased during the differentiation of 3T3-L1 preadipocytes into adipocytes (P < 0.001) and after treatments with TNF-alpha, IL-6, insulin, and dexamethasone (P < 0.01). In addition, circulating nesfatin-1 levels were higher in high-fat-fed mice (P < 0.05) and showed positive correlation with body mass index in human. We report that nesfatin-1 is a novel depot specific adipokine preferentially produced by sc tissue, with obesity- and food deprivation-regulated expression.
内脂素-1 是一种最近发现的厌食肽，来源于其前体蛋白非酯化脂肪酸/核结合蛋白 2（NUCB2）。尽管下丘脑对于维持能量平衡至关重要，但脂肪组织通过与外周器官和大脑通讯的脂肪因子，在代谢活动和能量平衡的整合中发挥重要作用。目前，尚无关于脂肪组织中内脂素-1 的表达、调节和分泌的数据。因此，我们研究了人脂肪组织和鼠脂肪组织中 NUCB2/内脂素-1 基因和蛋白的表达。此外，我们还通过定量 RT-PCR 和 Western blot 研究了胰岛素、地塞米松和炎性细胞因子的作用，以及禁食和肥胖对内脂素-1 表达的影响。我们提供的数据显示，与其他脂肪组织相比，sc 脂肪组织中的 NUCB2 mRNA（P < 0.001）、内脂素-1 细胞内蛋白（P < 0.001）和分泌（P < 0.01）均显著升高。此外，高脂肪喂养的小鼠中内脂素-1 蛋白表达显著增加（P < 0.01），而禁食时则显著减少（P < 0.01）。炎性细胞因子（TNFalpha 和 IL-6）、胰岛素和地塞米松刺激 sc 脂肪组织外植体，导致细胞内内脂素-1 水平显著增加。此外，我们还提供了证据表明，在 3T3-L1 前脂肪细胞分化为脂肪细胞的过程中（P < 0.001），以及在用 TNFalpha、IL-6、胰岛素和地塞米松处理后（P < 0.01），内脂素-1 分泌到培养基中的量显著增加。此外，高脂肪喂养的小鼠循环内脂素-1 水平升高（P < 0.05），并且与人体体重指数呈正相关。我们报告称，内脂素-1 是一种新型的脂肪组织特异性脂肪因子，主要由 sc 组织产生，其表达受肥胖和禁食调节。
