The distinct catabolic role of peroxisome proliferator-activated receptor delta (PPARδ) is reported in new research published in Genome Medicine, with therapeutic implications for type 2 diabetes, dyslipidemia, and metabolic syndrome.
Modulators of the α and γ members of the PPAR protein family are currently used to treat symptoms of metabolic syndrome. However, the specific metabolic effects caused by activating the third member of the family, PPARδ, are less well understood.
Julian Griffin and colleagues examine the physiological and pharmacological effects of a synthetic ligand which activates PPARδ in their article “Increased hepatic oxidative metabolism distinguishes the action of Peroxisome Proliferator-Activated Receptor delta from Peroxisome Proliferator-Activated Receptor gamma in the Ob/Ob mouse”.
The authors show that the activation of PPARδ has a different effect to that of its sister molecule PPARγ in obese mice. While both proteins have roles in improving glucose tolerance, PPARδ induced unique responses in liver and skeletal muscle tissues, switching from the lactic acid (Cori) cycle to ketone and fatty acid oxidative metabolism. This switch may contribute to the increased insulin sensitivity seen with PPARδ activation. These findings could give rise to further therapeutic applications for PPARδ agonists in the control of blood glucose and lipids.
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Assistant Editor, Genome Medicine