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Geun-Hyung Kang 1 Article
Diabetes, Obesity and Metabolism
The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE−/−FXR−/− Mice
Yenna Lee, Bo-Rahm Kim, Geun-Hyung Kang, Gwan Jae Lee, Young Joo Park, Haeryoung Kim, Hak Chul Jang, Sung Hee Choi
Endocrinol Metab. 2021;36(6):1243-1253.   Published online December 28, 2021
DOI: https://doi.org/10.3803/EnM.2021.1100
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  • 4 Citations
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   CrossRef-TDMCrossref - TDM
Background
Farnesoid X receptor (FXR), a bile acid–activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency.
Methods
En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)−/− and ApoE−/−FXR−/− mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice.
Results
Compared with ApoE−/− mice, ApoE−/−FXR−/− mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE−/−FXR−/− mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver).
Conclusion
Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.

Citations

Citations to this article as recorded by  
  • Whey protein hydrolysate alleviated atherosclerosis and hepatic steatosis by regulating lipid metabolism in apoE-/- mice fed a Western diet
    Kai Wang, Zixin Fu, Xiaoyi Li, Hui Hong, Xin Zhan, Xiaohong Guo, Yongkang Luo, Yuqing Tan
    Food Research International.2022; 157: 111419.     CrossRef
  • Melatonin alleviates PM 2.5 ‐induced glucose metabolism disorder and lipidome alteration by regulating endoplasmic reticulum stress
    Zhou Du, Junjie Hu, Lisen Lin, Qingqing Liang, Mengqi Sun, Zhiwei Sun, Junchao Duan
    Journal of Pineal Research.2022;[Epub]     CrossRef
  • Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia
    Joon Ho Moon, Kyuho Kim, Sung Hee Choi
    Endocrinology and Metabolism.2022; 37(4): 575.     CrossRef
  • The role of the gut microbiota in health and cardiovascular diseases
    Lu Wang, Shiqi Wang, Qing Zhang, Chengqi He, Chenying Fu, Quan Wei
    Molecular Biomedicine.2022;[Epub]     CrossRef

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