Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Biological and Chemical Engineering, Jiaxing University, Jiaxing, Zhejiang 314000, China.
College of Biological and Chemical Engineering, Jiaxing University, Jiaxing, Zhejiang 314000, China.
Exp Cell Res. 2018 Jun 1;367(1):15-23. doi: 10.1016/j.yexcr.2018.01.027. Epub 2018 Jan 31.
The C1q/TNF-related protein 6 (CTRP6) is an adipokine involved in diverse biological processes. Formerly, we identified that CTRP6 regulates adipocyte differentiation, fatty acid oxidation and triglyceride accumulation in vitro. However, the effects of CTRP6 on adiposity in vivo have not yet been defined. This study aimed to confirm the involvement of CTRP6 in adipose accumulation and brown adipogenesis by intraperitoneal injection of the CTRP6-shRNA lentivirus into mice (CL mice). CL mice were significantly thinner than the control mice after feeding with a high fat diet (HFD), independent of food intake quantity. These HFD-fed CL mice displayed lower white and brown adipocyte sizes, and serum leptin levels, but an increase in serum adiponectin and insulin sensitivity relative to control mice. Additionally, the brown fat markers, such as UCP1, PRDM16, PGC1α and Cidea were found to be upregulated in the white and brown adipose tissue of the CL mice. These markers were also upregulated in a primary culture of mouse white and brown adipocytes treated with the CTRP6-shRNA lentivirus. Mechanistically, the knockdown of CTRP6 increased p38MAPK phosphorylation, but decreased expression of proteins involved in the Hedgehog signaling pathway (Sufu, Gli2 and Gli3). CTRP6 knockdown also upregulated expression of mitochondrial metabolic factors NRF-1, TFAM, CPT1 and Cyt C. Data from the current study show that CTRP6 knockdown protects against diet-induced obesity and promotes brown adipogenesis by the p38MAPK/Hh signaling pathway in conjunction with the upregulation of brown fat markers and mitochondrial metabolic factors.
C1q/TNF 相关蛋白 6（CTRP6）是一种脂肪因子，参与多种生物学过程。此前，我们发现 CTRP6 可调节体外脂肪细胞分化、脂肪酸氧化和甘油三酯积累。然而，CTRP6 对体内肥胖的影响尚未确定。本研究旨在通过腹腔注射 CTRP6-shRNA 慢病毒确认 CTRP6 在脂肪堆积和棕色脂肪生成中的作用（CL 小鼠）。CL 小鼠在高脂饮食喂养后比对照小鼠明显更瘦，而不依赖于食物摄入量。这些 HFD 喂养的 CL 小鼠表现出较低的白色和棕色脂肪细胞大小，以及较低的血清瘦素水平，但血清脂联素水平升高和胰岛素敏感性增强，与对照小鼠相比。此外，在 CL 小鼠的白色和棕色脂肪组织中发现棕色脂肪标志物，如 UCP1、PRDM16、PGC1α 和 Cidea 上调。在经 CTRP6-shRNA 慢病毒处理的小鼠白色和棕色原代脂肪细胞培养物中，这些标志物也上调。从机制上讲，CTRP6 的敲低增加了 p38MAPK 磷酸化，但降低了 Hedgehog 信号通路（Sufu、Gli2 和 Gli3）中涉及的蛋白质的表达。CTRP6 敲低还上调了线粒体代谢因子 NRF-1、TFAM、CPT1 和 Cyt C 的表达。本研究的数据表明，CTRP6 敲低通过 p38MAPK/Hh 信号通路与上调棕色脂肪标志物和线粒体代谢因子来防止饮食诱导的肥胖并促进棕色脂肪生成。
