Fenofibrate prevents obesity and hypertriglyceridemia in low-density lipoprotein receptor-null mice.
Our previous study demonstrated that fenofibrate improves both lipid metabolism and obesity, in part through hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) activation, in female ovariectomized, but not in sham-operated, low-density lipoprotein receptor-null (LDLR-null) mice. The aim of this study was to determine whether fenofibrate prevents obesity and hypertriglyceridemia in male LDLR-null mice. Mice fed a high-fat diet for 8 weeks exhibited increases in body and white adipose tissue (WAT) weights and developed severe hypertriglyceridemia compared with mice fed a low-fat control diet. However, these effects were effectively prevented by fenofibrate. Mice given a fenofibrate-supplemented high-fat diet showed significantly reduced body weight, WAT weight, and serum triglycerides versus high-fat diet-fed animals. Triton WR1339 study showed that fenofibrate-induced reduction in circulating triglycerides was due to the decreased secretion of triglycerides from the liver. Moreover, the administration of fenofibrate not only resulted in liver hypertrophy and reduction in hepatic lipid accumulation, but also regulated the transcriptional expression of PPARalpha target genes, such as hepatic acyl-coenzyme A (CoA) oxidase and apolipoprotein C-III (apoC-III). Therefore, our results suggest that alterations in hepatic PPARalpha action by fenofibrate seem to suppress diet-induced obesity and severe hypertriglyceridemia caused by LDLR deficiency in male mice.
Jeong
Sunhyo
S
Department of Life Sciences, Mokwon University, Taejon, Korea.
Kim
Mina
M
Han
Miyoung
M
Lee
Hyunghee
H
Ahn
Jiwon
J
Kim
Moonza
M
Song
Yang-Heon
YH
Shin
Chuog
C
Nam
Ki-Hoan
KH
Kim
Tae Woo
TW
Oh
Goo Taeg
GT
Yoon
Michung
M
D042962:Acyl-CoA Oxidase / Q000096:biosynthesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001056:Apolipoproteins C / Q000096:biosynthesis / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D015228:Hypertriglyceridemia / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D001056:Apolipoproteins C; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D011973:Receptors, LDL; D014280:Triglycerides; D011092:Polyethylene Glycols; D002784:Cholesterol; D042962:Acyl-CoA Oxidase; D011345:Fenofibrate; C016811:tyloxapol