CMKLR1 deficiency attenuates androgen-induced lipid accumulation in mice.

	CMKLR1 deficiency attenuates androgen-induced lipid accumulation in mice.
	Zhao Huashan; Wu Linlin; Huang Chen; Xiang Liang; Wang Baobei; Xiao Tianxia; Li Mengxia; Ren Lirong; Niu Jianmin; Zhang Jian V.
刊名	Cellular Physiology and Biochemistry
	2018
文献子类	期刊论文
英文摘要	Background/Aims: Excess androgen-induced obesity has become a public health problem, and its prevalence has increased substantially in recent years. Chemokine-like receptor 1 (CMKLR1), a receptor of Chemerin secreted by adipose tissue, is linked to adipocyte differentiation, adipose tissue development and obesity. However, the effect of CMKLR1 signaling on androgen-mediated adiposity in vivo remains unclear. Methods: Combining CMKLR1 knockout mice, we constructed the androgen excess female mice model by treatment of 5α-dihydrotestosterone (DHT) and androgen deficiency male mice model by orchidectomy (ORX). For mechanism investigation, we employed 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA), a antagonist for CMKLR1, to suppress the CMKLR1 in vivo and wortmannin, a PI3K signaling antagonist, to treat BAT explants culture in vitro. Meanwhile, we used histological examination and qPCR method, as well as western blotting, glucose tolerance tests and biochemical analysis of serum, to detect the phenotypes and the change of gene expression. Results: We demonstrated that androgen excess in female mice resulted in a larger cell size in white adipose tissue (WAT) and brown adipose tissue (BAT), whereas androgen deprivation of male mice induced a smaller cell size. Both effects relating to the adipocytes size could be attenuated in CMKLR1 knockout mice. CMKLR1 deficiency influenced the effect of androgen on adipose tissue by regulating the mRNA expression of androgen receptor (AR) and adipocyte markers (such as Fabp4 and Cidea). Moreover, suppression of CMKLR1 by α-NETA can also weaken the enlargement of the adipocyte cell size caused by DHT. Furthermore, we found DHT could reduce the phosphorylated ERK (pERK) in BAT, while CMKLR1 inactivation inhibited this effect induced by DHT through PI3K signaling pathway. Conclusion: These findings reveal an anti-obesity role of CMKLR1 deficiency in regulating lipid accumulation, highlighting the scientific importance for further development of small molecule CMKLR1 antagonists as fundamental scientific tools or a potential drug for the treatment of adiposity.
URL标识	查看原文
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/14698]
专题	深圳先进技术研究院_医药所
推荐引用方式 GB/T 7714	Zhao Huashan,Wu Linlin,Huang Chen,et al. CMKLR1 deficiency attenuates androgen-induced lipid accumulation in mice.[J]. Cellular Physiology and Biochemistry,2018.
APA	Zhao Huashan.,Wu Linlin.,Huang Chen.,Xiang Liang.,Wang Baobei.,...&Zhang Jian V..(2018).CMKLR1 deficiency attenuates androgen-induced lipid accumulation in mice..Cellular Physiology and Biochemistry.
MLA	Zhao Huashan,et al."CMKLR1 deficiency attenuates androgen-induced lipid accumulation in mice.".Cellular Physiology and Biochemistry (2018).