Abstract
Obesity is characterized by increased fat mass, as adipose tissue serves as a storage site for excess energy from food consumption. In obesity, altered lipid metabolism of adipose tissue, characterized by fatty acid uptake, de novo lipogenesis, and lipolysis, are induced. In this study, we examined the effect of zerumbone, a major sesquiterpene from wild ginger, on high-fat diet (HF)-induced obesity and dysregulated lipid metabolism in the white adipose tissues (WAT) of C57BL/6N mice. Dietary supplementation with zerumbone ameliorated HF-induced obesity and improved impaired lipid metabolism in WAT. Zerumbone additionally induced AMPK activation and phosphorylation of acetyl-CoA carboxylase, and effectively decreased adipogenic differentiation, in a concentration-dependent manner in the 3T3-L1 cells. Dysregulated microRNAs in obese WAT and adipocytes were examined, and zerumbone treatment was found to effectively reverse the robust upregulation of microRNA-146b. An increase in the levels of SIRT1, the direct target of microRNA-146b, was observed in zerumbone-treated differentiated adipocytes. This increase was additionally observed in WAT of zerumbone-supplemented mice. The antiadipogenic effect of zerumbone was found to be abolished in SIRT1-silenced 3T3-L1 cells. The increase in SIRT1 levels induced by zerumbone led to deacetylation of FOXO1 and PGC1α in WAT and differentiated 3T3-L1 cells. These findings indicate that zerumbone ameliorated diet-induced obesity and inhibited adipogenesis, and that the underlying mechanisms involved AMPK and the microRNA-146b/SIRT1 pathway. Zerumbone may represent a potential therapeutic candidate for the prevention and treatment of metabolic diseases, particularly obesity.
Highlights
Obesity is an energy imbalance disorder in which nutrient intake chronically exceeds energy expenditure, resulting in the increased fat mass [1]
We examined the effect of zerumbone on high-fat diet-induced obesity and measured the expression levels of lipid metabolism-regulated genes in adipose tissue in mice and differentiated 3T3-L1 cells
The weight of epididymal white adipose tissue (WAT) was significantly reduced in the zerumbone-supplemented mice compared with the high-fat diet (HF) mice (P < 0.05)(Figure 1D)
Summary
Obesity is an energy imbalance disorder in which nutrient intake chronically exceeds energy expenditure, resulting in the increased fat mass [1]. The worldwide prevalence of obesity has more than doubled since 1980. According to WHO statistics, 39% of adults over 18 years old were overweight, and 13% were obese in 2014. Unless the current trend is reversed, the continuing increase in obesity will have detrimental effects on global health and economy. Despite advances in weight management strategies in recent years, the treatment of obesity remains a significant challenge. The potential of natural phytochemicals as substitutes for weight management [3] and their ability to increase fatty acid β-oxidation, fat absorption, and suppress appetite [4] have received much interest
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