Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans

doi:10.1038/s41419-019-1706-y

	Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans
	Wu, Lingyan 1,2; Xia, Mingfeng 3,4; Duan, Yanan 1; Zhang, Lina 1; Jiang, Haowen 1; Hu, Xiaobei 1; Yan, Hongmei 3,4; Zhang, Yiqiu 5; Gu, Yushen 5; Shi, Hongcheng 5
刊名	CELL DEATH & DISEASE
	2019-06-13
卷号	10 页码:18
ISSN号	2041-4889
DOI	10.1038/s41419-019-1706-y
通讯作者	Li, Jia(jli@simm.ac.cn) ; Gao, Xin(happy20061208@126.com) ; Li, Jingya(jyli@simm.ac.cn)
英文摘要	Brown adipose tissue (BAT) dissipates metabolic energy and mediates non-shivering thermogenesis, thereby boosting energy expenditure. Increasing BAT mass and activity is expected to be a promising strategy for combating obesity; however, few medications effectively and safely recruit and activate BAT in humans. Berberine (BBR), a natural compound, is commonly used as a nonprescription drug to treat diarrhea. Here, we reported that 1-month BBR intervention increased BAT mass and activity, reduced body weight, and improved insulin sensitivity in mildly overweight patients with non-alcoholic fatty liver disease. Chronic BBR treatment promoted BAT development by stimulating the expression of brown adipogenic genes, enhanced BAT thermogenesis, and global energy expenditure in diet-induced obese mice and chow-fed lean mice, Consistently, BBR facilitated brown adipocyte differentiation in both mouse and human primary brown preadipocytes. We further found that BBR increased the transcription of PRDM16, a master regulator of brown/beige adipogenesis, by inducing the active DNA demethylation of PRDM16 promoter, which might be driven by the activation of AMPK and production of its downstream tricarboxylic acid cycle intermediate alpha-Ketoglutarate. Moreover, chronic BBR administration had no impact on the BAT thermogenesis in adipose-specific AMPKa1 and AMPKa2 knockout mice. In summary, we found that BBR intervention promoted recruitment and activation of BAT and AMPK-PRDM16 axis was indispensable for the pro-BAT and pro-energy expenditure properties of BBR. Our findings suggest that BBR may be a promising drug for obesity and related metabolic disorders in humans partially through activating BAT.
资助项目	National Natural Science Foundation of China[81300682] ; National Natural Science Foundation of China[81873660] ; National Natural Science Foundation of China[81770865] ; National Natural Science Foundation of China[81125023] ; National Natural Science Foundation of China[81470166] ; Shanghai Health and Family Planning Commission Foundation[15GWZK0801] ; National Key Basic Research Program of China[2012CB524906] ; National Key Basic Research Program of China[2016YFC1305500] ; Municipal Science and Technology Committee[16411954800] ; Municipal Science and Technology Committee[15DZ2291600]
WOS关键词	BETA(3)-ADRENERGIC RECEPTOR AGONIST ; INSULIN SENSITIVITY ; ENERGY-EXPENDITURE ; PROTEIN-KINASE ; ADIPOCYTE ; OBESITY ; THERMOGENESIS ; METABOLISM ; MECHANISM ; L-796568
WOS研究方向	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000472436800004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289380]
专题	中国科学院上海药物研究所
通讯作者	Li, Jia; Gao, Xin; Li, Jingya
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Fudan Univ, Zhongshan Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China 4.Fudan Inst Metab Dis, Shanghai, Peoples R China 5.Fudan Univ, Zhongshan Hosp, Dept Nucl Med, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wu, Lingyan,Xia, Mingfeng,Duan, Yanan,et al. Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans[J]. CELL DEATH & DISEASE,2019,10:18.
APA	Wu, Lingyan.,Xia, Mingfeng.,Duan, Yanan.,Zhang, Lina.,Jiang, Haowen.,...&Li, Jingya.(2019).Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans.CELL DEATH & DISEASE,10,18.
MLA	Wu, Lingyan,et al."Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans".CELL DEATH & DISEASE 10(2019):18.