Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet
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 d...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2022.971581/full |
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| author | Ying Zhang Xiu-Bin Jia Yun-Chao Liu Wen-Qian Yu Yan-Hong Si Yan-Hong Si Shou-Dong Guo |
| author_facet | Ying Zhang Xiu-Bin Jia Yun-Chao Liu Wen-Qian Yu Yan-Hong Si Yan-Hong Si Shou-Dong Guo |
| author_sort | Ying Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T22:58:09Z |
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| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-04-12T22:58:09Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-b91c38df6a844ed096935acb83fe3a582022-12-22T03:13:08ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2022-09-01910.3389/fnut.2022.971581971581Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat dietYing Zhang0Xiu-Bin Jia1Yun-Chao Liu2Wen-Qian Yu3Yan-Hong Si4Yan-Hong Si5Shou-Dong Guo6College of Pharmacy and Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaCollege of Pharmacy and Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaCollege of Pharmacy and Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaInnovative Drug Research Centre, School of Pharmacy, Institute of Lipid Metabolism and Atherosclerosis, Weifang Medical University, Weifang, ChinaCollege of Pharmacy and Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaCollege of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaInnovative Drug Research Centre, School of Pharmacy, Institute of Lipid Metabolism and Atherosclerosis, Weifang Medical University, Weifang, ChinaObesity 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.https://www.frontiersin.org/articles/10.3389/fnut.2022.971581/fullobesityNAFLDtriglyceridePPARγ agonistfibrates |
| spellingShingle | Ying Zhang Xiu-Bin Jia Yun-Chao Liu Wen-Qian Yu Yan-Hong Si Yan-Hong Si Shou-Dong Guo Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet Frontiers in Nutrition obesity NAFLD triglyceride PPARγ agonist fibrates |
| title | Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet |
| title_full | Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet |
| title_fullStr | Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet |
| title_full_unstemmed | Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet |
| title_short | Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet |
| title_sort | fenofibrate enhances lipid deposition via modulating pparγ srebp 1c and gut microbiota in ob ob mice fed a high fat diet |
| topic | obesity NAFLD triglyceride PPARγ agonist fibrates |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2022.971581/full |
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