Peroxisome proliferator-activated receptors (PPARs) α, δ and γ are nuclear transcription factors that control key genes involved in fatty acid metabolism and energy homeostasis. Little is known about PPAR activation in vivo and the existence of overlapping functions between PPARα, -δ and -γ. As skeletal muscle is an important site for insulin action and acts as a significant sensor for life-style-induced influences in whole-body energy metabolism, we investigated the expression of PPARα, -δ and -γ in rat skeletal muscle in response to exercise after four- and twelve-weeks of high-fat feeding, respectively. PPARα mRNA expression in skeletal muscle increased in parallel with other signs of developing metabolic syndrome such as increased visceral fat pad volymes, plasma free fatty acids and muscle triglyceride concentrations. PPARα mRNA expression was up-regulated 3-fold after four weeks of high-fat feeding (p<0.01). Exercise reversed the high-fat induced increase in PPARα expression in young lean rats (p<0.05), but did not change the PPARα, -δ and -γ expression in the skeletal muscle in the normal nutritional state. The increase in PPARα expression declined during a longer term of high-fat feeding. In contrast, exercise increased PPARδ mRNA and protein expression 3- to 6-fold in skeletal muscle after longer-term high-fat feeding (p<0.05). This effect was accompanied by a reduction in skeletal muscle fat content. These findings suggest that parallel activation of PPARα and -δ expression in skeletal muscle may be an important adaptive mechanism in response to increased fatty acid loads in young, lean animals, protecting them from insulin resistance, whereas exercise might be needed to mediate the same positive effects in older animals.

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