Fenofibrate inhibits adipocyte hypertrophy and insulin resistance by activating adipose PPARalpha in high fat diet-induced obese mice.
10.3858/emm.2009.41.6.045
- Author:
Sunhyo JEONG
1
;
Michung YOON
Author Information
1. Department of Life Sciences, Mokwon University, Daejeon 302-729, Korea. yoon60@mokwon.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
adipocytes;
hyperglycemia;
hyperlipidemia;
insulin resistance;
PPARalpha
- MeSH:
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
- From:Experimental & Molecular Medicine
2009;41(6):397-405
- CountryRepublic of Korea
- Language:English
-
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.
