Exp Mol Med.  2002 Dec;34(6):481-488.

Fenofibrate regulates obesity and lipid metabolism with sexual dimorphism

• Yoon MC
• Jeong SH
• Nicol CJ
• Lee HH
• Han MY
• Kim JJ
• Seo YJ
• Ryu CY
• Oh GT

Abstract

To determine whether the PPARalpha 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 PPARalpha 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 alpha target genes encoding enzymes for fatty acid beta-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 beta-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 PPARalpha.

Keyword

fenofibrate; lipid; obesity; PPAR alpha; sex

MeSH Terms

Adipose Tissue/drug effects/metabolism
Animals
Body Composition/drug effects
Body Weight/drug effects
Diet
Dietary Fats/pharmacology
Female
Gene Expression Regulation/drug effects
Lipids/blood/*metabolism
Liver/drug effects/metabolism
Male
Mice
Mice, Inbred C57BL
Obesity/*metabolism/pathology
Organ Weight/drug effects
Procetofen/*pharmacology
Receptors, Cytoplasmic and Nuclear/*agonists
*Sex Characteristics
Time Factors
Transcription Factors/*agonists