Abstract
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.
MeSH terms
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Animals
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Bezafibrate / pharmacology*
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Blood Glucose / analysis
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Body Weight / drug effects
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Carrier Proteins / drug effects
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Carrier Proteins / genetics
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Cholesterol / metabolism
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Diabetes Mellitus, Experimental / complications
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Diabetes Mellitus, Experimental / drug therapy
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Diabetes Mellitus, Experimental / genetics
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Diabetes Mellitus, Type 2 / complications
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Diabetes Mellitus, Type 2 / drug therapy
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Diabetes Mellitus, Type 2 / genetics
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Dose-Response Relationship, Drug
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Eating / drug effects
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Fatty Acids / metabolism
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Gene Expression Regulation / drug effects
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Hypolipidemic Agents / pharmacology*
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Insulin / metabolism
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Ion Channels
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Leptin / metabolism
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Male
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Membrane Proteins / drug effects
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Membrane Proteins / genetics
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Membrane Transport Proteins / drug effects
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Membrane Transport Proteins / genetics
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Mitochondrial Proteins / drug effects
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Mitochondrial Proteins / genetics
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Obesity / drug therapy
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Obesity / etiology
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Obesity / genetics*
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PPAR alpha / drug effects
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PPAR alpha / genetics
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PPAR delta / drug effects
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PPAR delta / genetics
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RNA, Messenger / drug effects
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Rats
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Rats, Inbred Strains
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Thyroid Hormones / metabolism
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Uncoupling Agents*
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Uncoupling Protein 1
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Uncoupling Protein 2
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Uncoupling Protein 3
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Viscera / drug effects
Substances
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Blood Glucose
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Carrier Proteins
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Fatty Acids
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Hypolipidemic Agents
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Insulin
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Ion Channels
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Leptin
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Membrane Proteins
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Membrane Transport Proteins
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Mitochondrial Proteins
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PPAR alpha
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PPAR delta
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RNA, Messenger
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Thyroid Hormones
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Ucp2 protein, rat
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Ucp3 protein, rat
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Uncoupling Agents
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Uncoupling Protein 1
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Uncoupling Protein 2
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Uncoupling Protein 3
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Cholesterol
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Bezafibrate