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

Figure 3

PPARα receptor is essential for GW501516 induced weight loss and hepatic steatosis. (a) GW501516 dependent weight loss is not evident in PPARα-KO mice. (b) Both groups matched in their weekly food intake. (c) No significant difference was found in hepatic TG between PPARα-KO mice fed control or a diet supplemented with GW501516. (d) Nonfasted PPAR-KO mice had still detectable rise in plasma HDL when fed diet containing GW501516. (e) GW501516 activates PPARδ in PPARα-KO mice. mRNA levels of Plin2, a marker of PPARδ activation, were upregulated in PPARα-KO mice following feeding with a diet supplemented with GW501516. (f) mRNA expression level of hepatic Plin2 was not correlated with the level of liver TG. Each point on the graph represents mean value of each group for Plin2 relative expression and for mg/g of hepatic TG. Two more PPARδ target genes changed their mRNA expression level after treatment with GW501516 in PPARα-KO animals. Angptl4 (g) and Pdk4 (h) were upregulated in liver. Significance is indicated (; ; ), mice/group.

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