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

Abstract：

: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 α-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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Wu L,Xia M,Duan Y,Zhang L,Jiang H,Hu X,Yan H,Zhang Y,Gu Y,Shi H,Li J,Gao X,Li J

doi

10.1038/s41419-019-1706-y

subject

Has Abstract

pub_date

2019-06-13 00:00:00

pages

468

issue

6

issn

2041-4889

pii

10.1038/s41419-019-1706-y

journal_volume

10

pub_type

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