White adipose tissue (WAT) browning is a potential strategy to treat obesity, and is characterized by the formation of brown adipocytes induced by cold or beta-3 adrenergic receptor (beta-3AR) agonist treatment. The hedgehog (Hh) signaling at the primary cilium is closely related to obesity, and plays a key role in the differentiation and adipogenesis of adipocytes. However, little is known about its effects on WAT browning. In this study, browning models were used to evaluate the activity and effect of Hh signaling on WAT browning using Hh antagonists, agonist, and small-interfering RNAs (siRNAs) specific for glioma-associated oncogene homologue 1 (Gli1), smoothened (Smo), and suppressor of fused (Sufu). We observed that Hh signaling activity was inhibited during the browning process both in vivo and in vitro. Further, Hh signaling inhibition enhanced WAT browning, while its activation attenuated norepinephrine-induced browning. Thus, the inhibition of Hh signaling promotes WAT browning and therefore, Hh signaling may be a therapeutic target against obesity and associated comorbidities.
基金:
National Natural Science Foundation of China (81671359, 81770866, 81770837, 81900783), Jiangsu Provincial Medical Innovation Team (CXTDA2017001), Jiangsu Provincial Medical Youth Talent (QNRC2016083), Jiangsu Natural Science Foundation (BK20190139), General Project of China Postdoctoral Science Foundation (2019M651899).
第一作者机构:[1]Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Womens Hosp, Nanjing Maternal & Child Hlth Med Inst, Nanjing 210004, Peoples R China[2]Nanjing Med Univ, Dept Gastroenterol, Childrens Hosp, Nanjing 210008, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Womens Hosp, Nanjing Maternal & Child Hlth Med Inst, Nanjing 210004, Peoples R China[*1]Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Womens Hosp, 123 Tianfei St, Nanjing 210004, Peoples R China
推荐引用方式(GB/T 7714):
Zhang Zhuo,Zhang Xiao Xiao,Liu Zhi Feng,et al.Inhibition of hedgehog signaling promotes white adipose tissue browning[J].MOLECULAR AND CELLULAR ENDOCRINOLOGY.2020,518:doi:10.1016/j.mce.2020.110970.
APA:
Zhang, Zhuo,Zhang, Xiao Xiao,Liu, Zhi Feng,Guo, Xi Rong,Cui, Xian Wei...&Chi, Xia.(2020).Inhibition of hedgehog signaling promotes white adipose tissue browning.MOLECULAR AND CELLULAR ENDOCRINOLOGY,518,
MLA:
Zhang, Zhuo,et al."Inhibition of hedgehog signaling promotes white adipose tissue browning".MOLECULAR AND CELLULAR ENDOCRINOLOGY 518.(2020)