Fenofibrate regulates obesity and lipid metabolism with sexual dimorphism.
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 PPARalpha 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.
Yoon
Michung
M
Department of Life Sciences, Mokwon University, Taejon 302-729, Korea. yoon60@mokwon.ac.kr
Jeong
Sunhyo
S
Nicol
Christopher J
CJ
Lee
Hyunghee
H
Han
Miyoung
M
Kim
Jung-Jae
JJ
Seo
Yun-Jeong
YJ
Ryu
Chilyeol
C
Oh
Goo Taeg
GT
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D012727:Sex Characteristics; D013997:Time Factors; D014157:Transcription Factors / Q000819:agonists*
D004041:Dietary Fats; D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D011345:Fenofibrate