Expression of peroxisome proliferator-activated receptor α (PPARα) 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, PPARα/retinoid x receptor ligands, and FA all up-regulate PPARα 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. PPARα is a OB-R-dependent factor required for normal fat homeostasis in islet cells.
|Number of pages
|Proceedings of the National Academy of Sciences of the United States of America
|Published - Jul 21 1998
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