title: Fibrates reduce triacylglycerol content by upregulating adipose triglyceride lipase in the liver of rats.
abstract: Hepatic triacylglycerol (TAG) homeostasis is maintained by carefully regulated balance between its synthesis and disposal. Impairment in this balance causes steatosis. The aims of this study were i) to uncover whether fibrates control TAG concentration through the action of adipose triglyceride lipase (ATGL) and ii) to compare the potency of the effects on ATGL expression and TAG concentration among fenofibrate, bezafibrate, and clofibric acid in the liver of rats. Treatments of rats with the three fibrates induced ATGL and concomitantly decreased hepatic TAG concentration. The upregulation of ATGL was likely mediated through the activation of peroxisome proliferator-activated receptor α. Fibrates also expanded capacity of fatty acid β-oxidation. Importantly, three fibric acids (fenofibric, bezafibric, and clofibric acids) that are active metabolites formed in the liver exhibited almost the same potency to elevate ATGL expression in vivo, despite the fact that there were considerable differences in this regard among fenofibrate, bezafibrate, and clofibric acid when compared on the basis of their dosage. These results suggest that ATGL represents a potential therapeutic target for ameliorating hepatic steatosis and that fibric acids are promising agents to ameliorate and/or protect against hepatic steatosis.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Karahashi
authors.forename: Miki
authors.initials: M
authors.lastname: Hoshina
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Naomi
authors.initials: N
authors.lastname: Kudo
mesh_terms: D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology* / Q000627:therapeutic use; D002995:Clofibric Acid / Q000494:pharmacology* / Q000627:therapeutic use; D005234:Fatty Liver / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D008049:Lipase / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology* / Q000378:metabolism*; D008297:Male; D058990:Molecular Targeted Therapy; D047493:PPAR alpha / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D000217:Acyltransferases
chemical_list: D001629:Bezafibrate; D002995:Clofibric Acid; D011345:Fenofibrate; D008049:Lipase; D047493:PPAR alpha; D014280:Triglycerides; C571275:PNPLA2 protein, rat; D000217:Acyltransferases