Lentivirus-mediated CTRP6 silencing ameliorates diet-induced obesity in mice

Journal Article · Fri Jun 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.01.027· OSTI ID:23082371

Wu, Wenjing ^[1]; Zhang, Jin ^[2]; Zhao, Chen; Sun, Yunmei ^[1]; Yin, Yajun; Peng, Yongjia ^[2]; Pang, Weijun; Yang, Gongshe ^[1]

---

1. Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100 (China)
2. College of Biological and Chemical Engineering, Jiaxing University, Jiaxing, Zhejiang 314000 (China)

Highlights: • The knockdown of CTRP6 reduced both body weight and white adipose tissue of mice. • CTRP6 knockdown decreased the serum TG and improved the insulin sensitivity in mice. • The knockdown of CTRP6 promoted brown adipogenesis both in mice and in adipocytes. • CTRP6 knockdown activated p38MAPK but inhibited Hh signaling pathway in adipocytes. 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.

• OSTI ID: 23082371
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 367; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADIPOSE TISSUE
CARBOXYLIC ACIDS
INSULIN
INTRAPERITONEAL INJECTION
LEPTIN
METABOLIC DISEASES
MICE
MITOCHONDRIA
TRIGLYCERIDES