Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans
| Autor: | Ling-Yan Wu, Jing-Ya Li, Hongcheng Shi, Haowen Jiang, Hongmei Yan, Mingfeng Xia, Yiqiu Zhang, Ya-nan Duan, Xin Gao, Jia Li, Lina Zhang, Yushen Gu, Xiaobei Hu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cancer Research Berberine Adipose tissue AMP-Activated Protein Kinases Mice 0302 clinical medicine Adipose Tissue Brown Non-alcoholic Fatty Liver Disease Brown adipose tissue Adipocytes Medicine Promoter Regions Genetic Mice Knockout PRDM16 lcsh:Cytology Cell Differentiation Thermogenesis DNA-Binding Proteins medicine.anatomical_structure Adipogenesis 030220 oncology & carcinogenesis Knockout mouse Ketoglutaric Acids Adult medicine.medical_specialty Immunology Article 03 medical and health sciences Cellular and Molecular Neuroscience Insulin resistance Internal medicine Animals Humans Obesity lcsh:QH573-671 business.industry Body Weight AMPK Cell Biology DNA Methylation medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology Anti-Obesity Agents Insulin Resistance Energy Metabolism business Transcription Factors |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 10, Iss 6, Pp 1-18 (2019) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-019-1706-y |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|