Targeting PI3K/AKT signaling pathway in obesity

Obesity is a disorder with an increasing prevalence, which impairs the life quality of patients and intensifies societal health care costs. The development of safe and innovative prevention strategies and therapeutic approaches is thus of great importance. The complex pathophysiology of obesity involves multiple signaling pathways that influence energy metabolism in different tissues. The phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT) pathway is critical for the metabolic homeostasis and its function in insulin-sensitive tissues is described in the context of health, obesity and obesity-related complications. The PI3K family participates in the regulation of diverse physiological processes including but not limited to cell growth, survival, differentiation, autophagy, chemotaxis, and metabolism depending on the cellular context. AKT is downstream of PI3K in the insulin signaling pathway, and promotes multiple cellular processes by targeting a plethora of regulatory proteins that control glucose and lipid metabolism. Natural products are essential for prevention and treatment of many human diseases, including obesity. Anti-obesity natural compounds effect multiple pathophysiological mechanisms involved in obesity development. Numerous recent preclinical studies reveal the advances in using plant secondary metabolites to target the PI3K/AKT signaling pathway for obesity management. In this paper the druggability of PI3K as a target for compounds with anti-obesity potential is evaluated. Perspectives on the strategies and limitations for clinical implementation of obesity management using natural compounds modulating the PI3K/AKT pathway are suggested.