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Geniposide Improves Cholesterol Homeostasis by Regulating FXR-Mediated Liver-Gut Crosstalk of Bile Acids
38 Pages Posted: 15 Jun 2019
More...Abstract
Background: Hypercholesterolemia is the main risk factor for obesity and atherosclerosis and geniposide has been found to have hypolipidemic functions. However, the underlying mechanism is not clear.
Methods: The hypolipidemic action of geniposide was determined both in Wild type mice and ApoE-/- mice. Then hepatic lipid accumulation was analyzed via histomorphology analysis. The anti-atherosclerosis function of geniposide was performed in ApoE-/- mice. Moreover, the effects of geniposide on the synthesis and circulation of bile acids were analyzed by the total bile acids analysis and hepatic RNA-seq analysis, as well as the molecular analysis of related genes and proteins. Mechanistically, GW4064, an FXR agonist, is carried out to verify the potential mechanisms of geniposide in human HepG2 and Caco2 cells.
Findings: Geniposide accelerate the synthesis of bile acids through inactivating the negative feedback regulation of bile acids mediated by FXR in the liver, led to the enhancive reverse cholesterol transport and enhanced hypolipidemic function. What's more, geniposide reduces FXR-mediated reabsorption of bile acids in the ileum, thus resulted in the increasing excretion of bile acids.
Interpretations: Our study pointed out the regulatory functions of geniposide on FXR-mediated liver-gut crosstalk of bile acids and geniposide might be a novel strategy for maintaining cholesterol homeostasis.
Funding Statement: National Natural Science Foundation of China (31671890); Fundamental Research Funds for the Central Universities (No. JUSRP51708A and No. JUSRP11842); Jiangsu Key Laboratory of Advanced Food Manufacturing Equipment & Technology (FMZ201807); Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX19_1822).
Declaration of Interests: The authors declare that they have no competing interests.
Ethics Approval Statement: All the protocols of the study were approved by the Animal Ethics Committee of Jiangnan University.
Keywords: geniposide; cholesterol; bile acid; FXR; liver-gut crosstalk
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