Leptin: metabolic control and regulation

Abstract

Leptin, a protein released from adipose tissue, is being recognized to play an integral role in endocrine regulation of metabolism. While it is clearly evident that leptin is decreased during caloric restriction, the response of leptin to other types of stress has been plagued by conflicting data. With hypoglycemia stress, the literature may conflict because experimentally hypoglycemia is induced with infusion of insulin, an endocrine factor that can increase leptin levels. With exercise, leptin's response may depend on duration and intensity of exercise. While it has been clearly shown that the sympathetic nervous system (SNS) inhibits leptin secretion in a variety of experimental modes, the hypothalamic-pituitary-adrenal (HPA) axis may stimulate leptin secretion. This creates a paradox of leptin regulation during stress since both systems are activated with stress. If the SNS inhibition overrides the HPA axis' activation of leptin secretion, leptin's role during stress may be to allow a shifting of fuel consumption towards carbohydrate utilization. In type 1 diabetes mellitus, autonomic dysfunction may prevent the fall in leptin during stress. Although obesity is associated with type 2 diabetes mellitus, patients may have decreased leptin levels, especially when glucose is poorly controlled. This may contribute to further obesity and worsening of the disease. The purpose of this review to is critically analyze the literature regarding the impact of different types of stress on leptin secretion, the function of leptin during stress, and the role of leptin in the pathophysiology of diabetes.