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

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).

TrendsDeciphering the role of the antidiabetic effects of PPARβ/δ ligands may provide a basis for the development of medications for enhanced prevention and treatment of insulin resistance, T2DM, and CVD.PPARβ/δ ligands elicit antidiabetic effects in adipose tissue, liver, skeletal muscle, β cells, and the cardiovascular system.The antidiabetic effects of PPARβ/δ ligands result from their anti-inflammatory effects, ability to inhibit ER stress and hepatic lipogenesis, mimicking the adaptive responses to severe endurance training in skeletal muscle fiber composition, and improve atherogenesis and insulin secretion in insulin-resistant states.