Leptin in normal physiology and leptin resistance

Since the discovery of leptin as an adipokine in 1994, much progress has been made in the research about leptin. Circulating leptin binds to leptin receptor, activates STAT3-dependent and STAT3-independent signaling pathways, and plays an effective role in energy homeostasis, neuroendocrine function and metabolism mainly through acting on the central nervous system, especially the hypothalamus. Leptin resistance is considered as a key risk factor for obesity. Various mechanisms have been formulated in order to explain leptin resistance, including impairment in leptin transport, attenuation in leptin signaling, ER stress, inflammation and deficiency in autophagy. Here, we review our current knowledge about leptin action, leptin signaling and leptin resistance, hoping to provide new ideas for the battle against obesity.