Identification of isotschimgine as a novel farnesoid X receptor agonist with potency for the treatment of obesity in mice |
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| Affiliation: | 1. Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China;2. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China;1. College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian 116044, China;2. Liaoning Engineering Technology Centre of Target-based Nature Products for Prevention and Treatment of Ageing-related Neurodegeneration, Basic Medical College, Dalian Medical University, No. 9, South Road of Lvshun, Dalian 116044, China |
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| Abstract: | Obesity and its associated non-alcoholic fatty liver disease (NAFLD) have become epidemic medical problems worldwide; however, the current available therapeutic options are limited. Farnesoid X receptor (FXR) has recently emerged as an attractive target for obesity treatment. Here we demonstrate that isotschimgine (ITG), a constituent in genus Ferula, as a novel FXR agonist with anti-obesity and anti-hepatic steatosis effects. The results showed that ITG activated the FXR transactivity and bound with the ligand binding dormain (LBD) of FXR with gene reporter assays and AlphaScreen assays. In high-fat diet-induced obese (DIO) mice, ITG lowered body weight and fat mass, improved insulin resistance and hepatic steatosis. Mechanistic studies showed that ITG altered the expression levels of FXR downstream genes, lipid synthesis and energy metabolism genes in the liver of mice. Our findings suggest that ITG is a novel FXR agonist and may be a potential therapeutic choice for obesity associated with NAFLD. |
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| Keywords: | Isotschimgine Farnesoid X receptor Obesity Non-alcoholic fatty liver disease |
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