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Differential Regulation of Macrophage Peroxisome Proliferator–Activated Receptor Expression by Glucose

Abstract—Peroxisome proliferator–activated receptors (PPARs) are implicated in several metabolic disorders with altered glucose and lipid metabolism, including atherosclerosis and diabetes. In the present study, we evaluated the in vitro and ex vivo effects of high glucose concentrations on macrophage PPAR mRNA expression. Exposition of monocyte-derived macrophages isolated from healthy donors to a high glucose environment led to an increase in PPARα and PPARβ mRNA expression. In contrast, this treatment significantly decreased human macrophage PPARγ mRNA expression. Overexpression of PPARα and PPARβ mRNA and inhibition of PPARγ mRNA expression were also observed in monocyte-derived macrophages isolated from patients with type 2 diabetes. Because high glucose and PPARα agonists increase lipoprotein lipase (LPL) gene expression, the role of PPARα in the glucose-mediated upregulation of macrophage LPL gene expression was next evaluated. Incubation of murine J774 macrophages with high glucose concentrations ...