Xiao Xin-Hua, Qi Xiao-Yan, Wang Ya-Di, Ran Li, Yang Jing, Zhang Huan-Li, Xu Can-Xin, Wen Ge-Bo, Liu Jiang-Hua
Department of Metabolism and Endocrinology, University of South China, Hengyang, 421001, Hunan Province, China.
Department of Pathology & Immunology, Developmental, Regenerative and Stem Cell Biology, Washington University in St. Louis, MO, 63110, USA.
Biochem Biophys Res Commun. 2018 Feb 5;496(2):287-293. doi: 10.1016/j.bbrc.2018.01.039. Epub 2018 Jan 6.
Recent studies have highlighted recruiting and activating brite adipocytes in WAT (so-called "browning") would be an attractive anti-obesity strategy. Zinc alpha2 glycoprotein (ZAG) as an important adipokine, is reported to ameliorate glycolipid metabolism and lose body weight in obese mice. However whether the body reducing effect mediated by browning programme remains unclear. Here, we show that overexpression of ZAG in 3T3-L1 adipocytes enhanced expression of brown fat-specific markers (UCP-1, PRDM16 and CIDEA), mitochondrial biogenesis genes (PGC-1α, NRF-1/2 and mtTFA) and the key lipid metabolism lipases (ATGL, HSL, CPT1-A and p-acyl-CoA carboxylase). Additionally, those effects were dramaticlly abolished by H89/SB203580, revealing ZAG-induced browning depend on PKA and p38 MAPK signaling. Overall, our findings suggest that ZAG is a candidate therapeutic agent against obesity via induction of brown fat-like phenotype in white adipocytes.
最近的研究强调，在白色脂肪组织中招募并激活米色脂肪细胞（即所谓的“褐变”）将是一种有吸引力的抗肥胖策略。锌α2糖蛋白（ZAG）作为一种重要的脂肪因子，据报道可改善肥胖小鼠的糖脂代谢并减轻体重。然而，由褐变程序介导的体重减轻效果是否如此仍不清楚。在此，我们表明，在3T3-L1脂肪细胞中过表达ZAG可增强棕色脂肪特异性标志物（UCP-1、PRDM16和CIDEA）、线粒体生物发生基因（PGC-1α、NRF-1/2和mtTFA）以及关键脂质代谢脂肪酶（ATGL、HSL、CPT1-A和对-酰基辅酶A羧化酶）的表达。此外，H89/SB203580可显著消除这些作用，表明ZAG诱导的褐变依赖于PKA和p38 MAPK信号传导。总体而言，我们的研究结果表明，ZAG是一种通过诱导白色脂肪细胞产生棕色脂肪样表型来对抗肥胖的候选治疗剂。
