Abstract
The present study aimed to investigate whether scopolin exhibits beneficial effects on high-fat diet (HFD)-induced hepatic steatosis in mice. The involvement of sirtuin 1 (SIRT1) as a molecular target for scopolin was also explored. Scopolin decreased the Km of SIRT1 for p53 and nicotinamide adenine dinucleotide without altering Vmax in a cell-free system. Scopolin alleviated oleic acid-induced lipid accumulation and downregulation of SIRT1 activity in HepG2 cells, and these beneficial effects of scopolin were abolished in the presence of SIRT1 inhibitor. Mice administered 0.02% scopolin for 8 weeks exhibited improved phenotypes of HFD-induced hepatic steatosis along with increased hepatic SIRT1 activity and protein expression. Scopolin resulted in increased deacetylation of sterol regulatory element-binding protein 1c with subsequent downregulation of lipogenic genes, and enhanced deacetylation of protein peroxisome proliferator-activated receptor-γ coactivator 1α with upregulation of fatty acid oxidation genes in livers. Scopolin also enhanced deacetylation of nuclear factor-kappa enhancer binding protein and liver kinase B1 (LKB1), facilitating LKB1/AMP-activated protein kinase signaling cascades. Scopolin attenuated hepatic steatosis through activation of SIRT1-mediated signaling cascades, a potent regulator of lipid homeostasis. Increased hepatic SIRT1 activity and protein expression appeared to be associated with these beneficial effects of scopolin.
Highlights
The present study aimed to investigate whether scopolin exhibits beneficial effects on high-fat diet (HFD)-induced hepatic steatosis in mice
We previously reported that A. iwayomogi extract, mainly consisting of scopolin (1.21% w/w) along with other compounds such as scopoletin (0.38% w/w) and acetophenone glycoside (0.26% w/w) reversed high-fat diet (HFD)-induced abnormal increments in visceral adiposity, hepatic steatosis, and hyperlipidemia in mice[15]
The present study investigated whether scopolin isolated from A. iwayomogi exerts beneficial effects on HFD-induced hepatic steatosis in mice
Summary
The present study aimed to investigate whether scopolin exhibits beneficial effects on high-fat diet (HFD)-induced hepatic steatosis in mice. Scopolin resulted in increased deacetylation of sterol regulatory element-binding protein 1c with subsequent downregulation of lipogenic genes, and enhanced deacetylation of protein peroxisome proliferator-activated receptor-γ coactivator 1α with upregulation of fatty acid oxidation genes in livers. In hepatocytes with prolonged TG accretion, nuclear factor-kappa enhancer binding protein (NF-κB) that functions as a proinflammatory master switch is activated, leading to a subacute inflammatory response These pathways involved in the regulation of hepatic lipid metabolism and inflammation share a common regulator, sirtuin 1 (SIRT1) that is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase localized exclusively in the nucleus[1]. The present study investigated whether scopolin isolated from A. iwayomogi exerts beneficial effects on HFD-induced hepatic steatosis in mice. We explored the potential involvement of SIRT1 as a molecular target for scopolin in the process of reducing hepatic lipid accumulation
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