AUTHOR=Zhang Ying , Jia Xiu-Bin , Liu Yun-Chao , Yu Wen-Qian , Si Yan-Hong , Guo Shou-Dong TITLE=Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet JOURNAL=Frontiers in Nutrition VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.971581 DOI=10.3389/fnut.2022.971581 ISSN=2296-861X ABSTRACT=

Obesity is characterized by lipid accumulation in distinct organs. Presently, fenofibrate is a commonly used triglyceride-lowering drug. This study is designed to investigate whether long-term fenofibrate intervention can attenuate lipid accumulation in ob/ob mouse, a typical model of obesity. Our data demonstrated that fenofibrate intervention significantly decreased plasma triglyceride level by 21.0%, increased liver index and hepatic triglyceride content by 31.7 and 52.1%, respectively, and elevated adipose index by 44.6% compared to the vehicle group. As a PPARα agonist, fenofibrate intervention significantly increased the expression of PPARα protein in the liver by 46.3% and enhanced the expression of LDLR protein by 3.7-fold. However, fenofibrate dramatically increased the expression of PPARγ and SREBP-1c proteins by ~2.1- and 0.9-fold in the liver, respectively. Fenofibrate showed no effects on the expression of genes-related to fatty acid β-oxidation. Of note, it significantly increased the gene expression of FAS and SCD-1. Furthermore, fenofibrate modulated the gut microbiota. Collectively, long-term fenofibrate induces lipid accumulation in liver and adipose tissues in ob/ob mice by enhancing the expression of adipogenesis-related proteins and gut microbiota. These data suggest that fenofibrate may have limited effects on attenuating lipid deposition in obese patients.