Abstract
Expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and enzymes of fatty acid (FA) oxidation is markedly reduced in the fat-laden, dysfunctional islets of obese, prediabetic Zucker diabetic fatty (fa/fa) rats with mutated leptin receptors (OB-R). Leptin, PPARalpha/retinoid x receptor ligands, and FA all up-regulate PPARalpha and enzymes of FA oxidation and stimulate [3H]-palmitate oxidation in normal islets but not in islets from fa/fa rats. Overexpression of normal OB-R in islets of fa/fa rats corrects all of the foregoing abnormalities and reverses the diabetic phenotype. PPARalpha is a OB-R-dependent factor required for normal fat homeostasis in islet cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Clofibrate / metabolism
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Clofibrate / pharmacology
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DNA Primers
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Gene Expression Regulation / drug effects
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Islets of Langerhans / physiopathology*
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Leptin
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Male
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Pancreatic Diseases / physiopathology*
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Proteins / pharmacology
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Rats
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Rats, Mutant Strains
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Cytoplasmic and Nuclear / physiology*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Tretinoin / metabolism
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Tretinoin / pharmacology
Substances
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DNA Primers
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Leptin
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Proteins
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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Tretinoin
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Clofibrate