Fenofibrate Prevents Obesity and Hypertriglyceridemia in Low-Density Lipoprotein Receptor-Null Mice

Sunhyo Jeong, Mina Kim, Miyoung Han, Hyunghee Lee, Jiwon Ahn, Moonza Kim, Yang Heon Song, Chuog Shin, Ki Hoan Nam, Tae Woo Kim, Goo Taeg Oh, Michung Yoon

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40 Scopus citations


Our previous study demonstrated that fenofibrate improves both lipid metabolism and obesity, in part through hepatic peroxisome proliferator-activated receptor α (PPARα) 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 PPARα target genes, such as hepatic acyl-coenzyme A (CoA) oxidase and apolipoprotein C-III (apoC-III). Therefore, our results suggest that alterations in hepatic PPARα action by fenofibrate seem to suppress diet-induced obesity and severe hypertriglyceridemia caused by LDLR deficiency in male mice.

Original languageEnglish
Pages (from-to)607-613
Number of pages7
JournalMetabolism: Clinical and Experimental
Issue number5
StatePublished - May 2004

Bibliographical note

Funding Information:
Supported by Grant No. KRF-2003-015-C00621 from the Korea Research Foundation and by a grant of the Molecular and Cellular Biodiscovery Research Group (M101 06000094-01A200002400) from MOST.


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