Abstract
To determine whether the PPARα agonist fenofibrate regulates obesity and lipid metabolism with sexual dimorphism, we examined the effects of fenofibrate on body weight, white adipose tissue (WAT) mass, circulating lipids, and the expression of PPARα target genes in both sexes of high fat diet-fed C57BL/6J mice. Both sexes of mice fed a high-fat diet for 14 weeks exhibited increases in body weight, visceral WAT mass, as well as serum triglycerides and cholesterol, although these effects were more pronounced among males. Feeding a high fat diet supplemented with fenofibrate (0.05% w/w) reduced all of these effects significantly in males except serum cholesterol level. Females on a fenofibrate-enriched high fat diet had reduced serum triglyceride levels, albeit to a smaller extent compared to males, but did not exhibit decreases in body weight, WAT mass, and serum cholesterol. Fenofibrate treatment resulted in hepatic induction of PPAR α target genes encoding enzymes for fatty acid β-oxidation, the magnitudes of which were much higher in males compared to females, as evidenced by results for acyl-CoA oxidase, a first enzyme of the β-oxidation system. These results suggest that observed sexually dimorphic effects on body weight, WAT mass and serum lipids by fenofibrate may involve sexually related elements in the differential activation of PPARα.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Yoon, M., Jeong, S., Nicol, C. et al. Fenofibrate regulates obesity and lipid metabolism with sexual dimorphism. Exp Mol Med 34, 481–488 (2002). https://doi.org/10.1038/emm.2002.67
Published:
Issue Date:
DOI: https://doi.org/10.1038/emm.2002.67
Keywords
This article is cited by
-
Fenofibrate alleviates insulin resistance by reducing tissue inflammation in obese ovariectomized mice
Nutrition & Diabetes (2023)
-
Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen
Scientific Reports (2016)
-
Acyl-coenzyme A oxidases 1 and 3 in brown trout (Salmo trutta f. fario): Can peroxisomal fatty acid β-oxidation be regulated by estrogen signaling?
Fish Physiology and Biochemistry (2016)
-
Metabolomic analysis of simvastatin and fenofibrate intervention in high-lipid diet-induced hyperlipidemia rats
Acta Pharmacologica Sinica (2014)
-
Profile of Serum Bile Acids in Noncholestatic Volunteers: Gender-Related Differences in Response to Fenofibrate
Clinical Pharmacology & Therapeutics (2011)