Bezafibrate-induced changes over time in the expression of uncoupling protein (UCP) mRNA in the tissues: a study in spontaneously type 2 diabetic rats with visceral obesity.
The effect of short-term bezafibrate (BF) administration over time on the expression of UCP mRNA in the tissues was examined in Otsuka Long Evans Tokushima Fatty (OLETF) rats. Eight-week-old rats were divided into a high-dose (100 mg/kg) BF group (n = 15), a low-dose (10 mg/kg) BF group (n = 15) and a control group (n = 15), and followed for 14 days. Feed intake by the high-dose BF group increased significantly between days 10 and 14 of administration. Triglyceride, free fatty acid, and T(4) levels decreased significantly in a dose-dependent manner in the high-dose BF group. Leptin and insulin levels significantly decreased on days 3 and 7. Throughout the study period, liver UCP2 mRNA increased in the high-dose BF group. On day 3 of BF administration, the levels of UCP2 mRNA expression in the skeletal muscles as well as UCP3 mRNA expression in the WAT were significantly increased in the high-dose BF group. PPAR-alpha mRNA significantly increased in the liver on day 3 of BF administration. We thus conclude that the PPAR-alpha-mediated effects of BF on the expression of liver UCP2 may be one of the factors that helped to decrease insulin levels.
Mori
Yutaka
Y
Department of Internal Medicine, National Hospital Organization, Utsunomiya National Hospital, 2160 Shimookamoto, Kawachi-machi, Kawachi-gun, Tochigi 329-1193, Japan. moriyutakajp@yahoo.co.jp
Tokutate
Yoshiki
Y
Oana
Fumiki
F
Matsuzawa
Akane
A
Akahane
Satoshi
S
Tajima
Naoko
N
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007473:Ion Channels; D020738:Leptin / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000235:genetics; D009765:Obesity / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D047493:PPAR alpha / Q000187:drug effects / Q000235:genetics; D047494:PPAR delta / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000378:metabolism; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D014781:Viscera / Q000187:drug effects
D001786:Blood Glucose; D002352:Carrier Proteins; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D047494:PPAR delta; D012333:RNA, Messenger; D013963:Thyroid Hormones; C000604391:Ucp2 protein, rat; C000604394:Ucp3 protein, rat; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D002784:Cholesterol; D001629:Bezafibrate