PPARα Is Required for PPARδ Action in Regulation of Body Weight and Hepatic Steatosis in Mice

Figure 2

GW501516 stimulated hepatic triglyceride accumulation is mediated through PPARδ action. (a) Transgene expression in liver and muscle in non-tg, hPPARδ, and hPPARδΔAF2 animals in 2 weeks. (b) Body fat change determined by Magnetic Resonance Imaging (MRI) in animals fed control diet or diet supplemented with GW501516 in 2 weeks. (c) Liver fat content increased in mice overexpressing hPPARδ and treated with GW501516 in comparison to controls (). Mice overexpressing hPPARδΔAF2 (treated animals) accumulated less fat in the liver than control animals (). (d) mRNA levels of Plin2, a protein marker of TG accumulation and direct PPARδ responsive gene, are significantly correlated with hepatic TG levels. Each point on the graph represents mean value of each group (control and treated) for Plin2 relative expression versus mg/g of hepatic TG. (e) Gene expressions in livers of nontransgenic and hPPARδ mice. Lipogenic master gene PPARγ was downregulated () in GW501516 treated hPPARδ animals, whereas β-oxidation enzyme Acox1 was upregulated () (hPPARδ). All genes were normalized to 18s RNA. mice/group, tested by two-way ANOVA.

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