Roles of leptin and resistin in metabolism, reproduction, and leptin resistance

Increased adipose mass can cause insulin resistance and type 2 diabetes mellitus. This phenomenon is related to adipocyte-secreted signaling molecules that affect glucose balance, such as fatty acids, adiponectin, leptin, interleukin-6, tumor necrosis factor-α, and resistin. Among these hormones, leptin and resistin play important roles in regulating weight and glucose metabolism. Leptin and resistin work in both similar and opposite ways, and they interact with each other. Circulating concentrations of leptin and resistin are elevated in models of obesity and rodents fed a high-fat diet. In addition, leptin and resistin are similarly regulated by nutritional status: they are reduced by fasting and increased by feeding. This effect is mediated partially through insulin receptors and glucose transporters. Our latest data provided the first indication that in sheep, intravenous infusion of resistin increases the mean circulating concentrations of leptin and decreases luteinizing hormone in a dose-dependent manner during both the long-day (LD) and short-day seasons. Furthermore, exogenous resistin increased suppressor of cytokine signaling (SOCS)-3 mRNA expression only during the LD season, when the leptin resistance/insensitivity phenomenon was observed in the arcuate nucleus, preoptic area, and anterior pituitary. We concluded that one factor contributing to central leptin resistance is autosuppression, via which leptin and resistin stimulate the expression of SOCS-3, which inhibits leptin signaling. The increased expression of SOCS-3 in response to leptin and resistin may be a pivotal cause of leptin resistance/insensitivity, a pathological situation in obese individuals and a physiological occurrence in sheep during the LD season.