Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice.
Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice.
Jeong
Sunhyo
S
Department of Life Sciences, Mokwon University, Taejon, Korea.
Han
Miyoung
M
Lee
Hyunghee
H
Kim
Mina
M
Kim
Jaekwang
J
Nicol
Christopher J
CJ
Kim
Bang Hyun
BH
Choi
Jae Hoon
JH
Nam
Ki-Hoan
KH
Oh
Goo Taeg
GT
Yoon
Michung
M
D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000187:drug effects; D000818:Animals; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D020738:Leptin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*
D004041:Dietary Fats; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D020738:Leptin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D011345:Fenofibrate