PPARδ as a therapeutic target in metabolic disease

Abstract 

PPARδ is the only member in the PPAR subfamily of nuclear receptors that is not a target of current drugs. Animal studies demonstrate PPARδ activation exerts many favorable effects, including reducing weight gain, increasing skeletal muscle metabolic rate and endurance, improving insulin sensitivity and cardiovascular function and suppressing atherogenic inflammation. These activities stem largely from the ability of PPARδ to control energy balance, reduce fat burden and protect against lipotoxicity caused by ectopic lipid deposition. Therefore, PPARδ represents a novel therapeutic target and the development of PPARδ gonists/modulators may be useful for treating the whole spectrum of metabolic syndrome.

Abbreviations: PPAR, peroxisome proliferator-activated receptor, FA, fatty acid, ADRP, adipose differentiation-related protein, AOX, acyl-CoA oxidase, CPT1, carnitine palmitoyltransferase 1, LCAD, long chain acyl-CoA dehydrogenase, PGC-1β, peroxisome proliferators-activated receptor γ co-activator 1β, GLUT4, glucose transport 4, FAS, fatty acid synthase, ACC, acetyl-CoA carboxylase, NASH, non-alcoholic steaohepatitis, IBD, Inflammatory bowel disease, COX II, cytochrome oxidase II, PDK4, pyruvate dehydrogenase kinase 4, PDK1, 3-phosphoinositide-dependent 3-kinase, ILK, integrin-linked kinase, ATGL, adipose triglyceride lipase, L-FABP, liver fatty acid binding protein, Ihh, Indian hedgehog

Keywords: Nuclear receptor, PPARδ, Obesity, Energy balance, Metabolic disease