期刊
CELLS
卷 10, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/cells10051126
关键词
obesity; adipogenesis; mitochondrial function; adipose tissue; sirtuins
类别
资金
- Italian Ministry of Health [GR-2013-02357959]
- MIUR [2017A5TXC3]
- Sapienza University [RM11816436436622, RM11916B7AD6D51F]
- Fondazione Internazionale D'Amato Onlus
The inhibition of SIRT5 stimulates brown adipogenesis in vitro, promoting the expression of brown adipocyte and mitochondrial markers and increasing lipolysis. This approach shows potential as a strategy to target obesity and type 2 diabetes by activating brown adipose tissue.
Brown adipose tissue (BAT) activity plays a key role in regulating systemic energy. The activation of BAT results in increased energy expenditure, making this tissue an attractive pharmacological target for therapies against obesity and type 2 diabetes. Sirtuin 5 (SIRT5) affects BAT function by regulating adipogenic transcription factor expression and mitochondrial respiration. We analyzed the expression of SIRT5 in the different adipose depots of mice. We treated 3T3-L1 preadipocytes and mouse primary preadipocyte cultures with the SIRT5 inhibitor MC3482 and investigated the effects of this compound on adipose differentiation and function. The administration of MC3482 during the early stages of differentiation promoted the expression of brown adipocyte and mitochondrial biogenesis markers. Upon treatment with MC3482, 3T3-L1 adipocytes showed an increased activation of the AMP-activated protein kinase (AMPK), which is known to stimulate brown adipocyte differentiation. This effect was paralleled by an increase in autophagic/mitophagic flux and a reduction in lipid droplet size, mediated by a higher lipolytic rate. Of note, MC3482 increased the expression and the activity of adipose triglyceride lipase, without modulating hormone-sensitive lipase. Our findings reveal that SIRT5 inhibition stimulates brown adipogenesis in vitro, supporting this approach as a strategy to stimulate BAT and counteract obesity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据