Exp Mol Med.  2009 Jun;41(6):397-405. 10.3858/emm.2009.41.6.045.

Fenofibrate inhibits adipocyte hypertrophy and insulin resistance by activating adipose PPARalpha in high fat diet-induced obese mice

Affiliations
  • 1Department of Life Sciences, Mokwon University, Daejeon 302-729, Korea. yoon60@mokwon.ac.kr

Abstract

Peroxisome proliferator-activated receptor alpha (PPARalpha) activation in rodents is thought to improve insulin sensitivity by decreasing ectopic lipids in non-adipose tissues. Fenofibrate, a lipid-modifying agent that acts as a PPARalpha agonist, may prevent adipocyte hypertrophy and insulin resistance by increasing intracellular lipolysis from adipose tissue. Consistent with this hypothesis, fenofibrate decreased visceral fat mass and adipocyte size in high fat diet-fed obese mice, and concomitantly increased the expression of PPARalpha target genes involved in fatty acid beta-oxidation in both epididymal adipose tissue and differentiated 3T3-L1 adipocytes. However, mRNA levels of adipose marker genes, such as leptin and TNFalpha, were decreased in epididymal adipose tissue by fenofibrate treatment. Fenofibrate not only reduced circulating levels of free fatty acids and triglycerides, but also normalized hyperinsulinemia and hyperglycemia in obese mice. Blood glucose levels of fenofibrate-treated mice were significantly reduced during intraperitoneal glucose tolerance test compared with obese controls. These results suggest that fenofibrate-induced fatty acid beta-oxidation in visceral adipose tissue may be one of the major factors leading to decreased adipocyte size and improved insulin sensitivity.

Keyword

adipocytes; hyperglycemia; hyperlipidemia; insulin resistance; PPARalpha

MeSH Terms

3T3 Cells
Adipocytes/cytology/*drug effects
Animals
Antilipemic Agents/*pharmacology
Blood Glucose
Body Weight
Cell Enlargement/*drug effects
Dietary Fats
Gene Expression Regulation/drug effects
Glucose Tolerance Test
Insulin/blood
*Insulin Resistance
Leptin/genetics
Lipids/blood
Mice
Mice, Inbred C57BL
Mice, Obese
PPAR alpha/*metabolism
Procetofen/*pharmacology
Tumor Necrosis Factor-alpha/genetics
Full Text Links
  • EMM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr