Abstract
SIRT1 plays a key role in regulating metabolism, and SIRT1 activation may be a promising strategy to treat metabolic syndrome. This study investigated whether zerumbone ameliorated diet‐induced obesity through SIRT1 activation. We used differentiated 3T3‐L1 fibroblasts to examine the effect of zerumbone on adipogenesis through the miR‐146b‐SIRT1 cascade. To investigate the anti‐obesity effect of zerumbone in vivo, we fed zerumbone to high‐fat diet‐induced obese C57BL/6J mice for 8 weeks and measured body weight, adipose tissue size, and blood lipid profiles. We also measured the effect of zerumbone supplementation on SIRT1 and AMPK signaling pathways in the white adipose tissue of these mice. Zerumbone inhibited adipogenesis through the miR146b‐SIRT1 pathway and significantly reduced diet‐induced obesity in mice. Zerumbone supplementation was associated with miR‐146b downregulation, followed by SIRT1 activation and the deacetylation of FOXO1 and PGC1α, respectively, in the white adipose tissue of these mice. Zerumbone also activated AMPK and modulated lipid metabolism in adipose tissue by increasing fatty acid oxidation and reducing adipogenesis gene expression, respectively. Zerumbone inhibited adipogenesis via the miR‐146b/SIRT1 pathway and ameliorated diet‐induced obesity in mice via SIRT1 activation, suggesting that zerumbone could target obesity‐related metabolic disorders through its stimulation of SIRT1 activity.
Published Version
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