β-Lapachone Prevents Diet-Induced Obesity by Increasing Energy Expenditure and Stimulating the Browning of White Adipose Tissue via Downregulation of miR-382 Expression

Abstract

There has been great interest in the browning of fat for the treatment of obesity. Although b-lapachone (BLC) has potential therapeutic effects on obesity, the fat-browning effect and thermogenic capacity of BLC on obesity have never been demonstrated. Here, we showed that BLC stimulated the browning of white adipose tissue (WAT), increased the expression of brown adipocyte-specific genes (e.g., uncoupling protein 1 [UCP1]), decreased body weight gain, and ameliorated metabolic parameters in mice fed a high-fat diet. Consistently, BLC-treated mice showed significantly higher energy expenditure compared with control mice. In vitro, BLC increased the expression of brown adipocyte-specific genes in stromal vascular fraction-differentiated adipocytes. BLC also controlled the expression of miR-382, which led to the upregulation of its direct target, Dio2. Upregulation of miR-382 markedly inhibited the differentiation of adipocytes into beige adipocytes, whereas BLC recovered beige adipocyte differentiation and increased the expression of Dio2 and UCP1. Our findings suggest that the BLC-mediated increase in the browning of WAT and the thermogenic capacity of BAT significantly results in increases in energy expenditure. Browning of WAT by BLC was partially controlled via the regulation of miR-382 targeting Dio2 and may lead to the prevention of diet-induced obesity.

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2

“…Therefore, we proposed that increased expression of miR-382 may promote LPCs differentiation. Occasionally, according to previous reports, miR-382 affect various lineage conversion, including adipocytes differentiation [32], osteogenic differentiation [33] and hematopoietic stem cell differentiation [34]. Together with our findings, we speculate that miR-382 is always involved in various stem cell differentiation.…”

Beneficial Metabolic Effects of Chitosan and Chitosan Oligosaccharide on Epididymal WAT Browning and Thermogenesis in Obese Rats

“…We found that the expression of Dio2 and PPARγ was increased in the epididymal fat of CTS-, COST-, and COSM-treated rats compared with the rats in the HF group ( Supplementary Figure S2D,E). Another argument is that Dio2 and PPARγ also play an important role in promoting browning [36], as PPARγ is essential for maintaining WAT and BAT differentiation [37] and Dio2 activation promotes adrenergic response and energy expenditure [38].…”

MicroRNAs as regulators of mitochondrial dysfunction and obesity

“…miR-378 is increased during brown adipocyte differentiation, promoting brown adipogenesis and protecting against both genetic and high-fat diet-induced obesity. Upregulation of miR-382 inhibited beige differentiation of mice WAT stromal vascular fractions, thereby reducing UCP1 mRNA and protein levels (18). On the other hand, miR-196a induced the beigening of mice WAT with characteristic appearance and gene expression profile of brown adipocytes (Prdm16 and Ucp1) (74).…”