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Trends Endocrinol Metab. 2016 May;27(5):319-334. doi: 10.1016/j.tem.2016.02.008. Epub 2016 Mar 20.

Unraveling the Effects of PPARβ/δ on Insulin Resistance and Cardiovascular Disease.

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Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Pediatric Research Institute, Hospital Sant Joan de Déu, Barcelona, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Diseases (CIBERDEM)-Instituto de Salud Carlos III, Diagonal 643, 08028 Barcelona, Spain. Electronic address:


Insulin resistance precedes dyslipidemia and type 2 diabetes mellitus (T2DM) development. Preclinical evidence suggests that peroxisome proliferator-activated receptor (PPAR) β/δ activators may prevent and treat obesity-induced insulin resistance and T2DM, while clinical trials highlight their potential utility in dyslipidemia. This review summarizes recent mechanistic insights into the antidiabetic effects of PPARβ/δ activators, including their anti-inflammatory actions, their ability to inhibit endoplasmic reticulum (ER) stress and hepatic lipogenesis, and to improve atherogenesis and insulin sensitivity, as well as their capacity to activate pathways that are also stimulated by exercise. Findings from clinical trials are also examined. Dissecting the effects of PPARβ/δ ligands on insulin sensitivity and atherogenesis may provide a basis for the development of therapies for the prevention and treatment of T2DM and cardiovascular disease (CVD).


PPARβ/δ; inflammation; insulin resistance; type 2 diabetes mellitus

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