Oncotarget

Research Papers: Pathology:

Zerumbone ameliorates high-fat diet-induced adiposity by restoring AMPK-regulated lipogenesis and microRNA-146b/SIRT1-mediated adipogenesis

Jiyun Ahn, Hyunjung Lee, Chang Hwa Jung, Won Hee Choi and Tae Youl Ha _

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Oncotarget. 2017; 8:36984-36995. https://doi.org/10.18632/oncotarget.16974

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Abstract

Jiyun Ahn1,2, Hyunjung Lee1, Chang Hwa Jung1,2, Won Hee Choi1 and Tae Youl Ha1,2

1 Research Group of Metabolic Mechanism, Korea Food Research Institute, Seongnam, Korea

2 Division of Food Biotechnology, University of Science & Technology, Daejeon, Korea

Correspondence to:

Tae Youl Ha, email:

Keywords: obesity; zerumbone; SIRT1; microRNA-146b; adipogenesis; Pathology Section

Received: October 24, 2016 Accepted: March 14, 2017 Published: April 08, 2017

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.


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