Leptin and Body Weight Regulation
L. ARTHUR CAMPFIELD
Leptin (also known as OB protein) is a protein hormone, encoded by the ob gene, produced primarily by adipocytes and secreted into the circulation, where it binds to a family of binding proteins. Leptin enters the brain through a specific receptor-mediated transport system in brain microvessels and acts on specific brain areas involved in the control of food intake and the regulation of energy balance. It acts through a specific membrane receptor, OB-RL, to alter ongoing brain processes, descending autonomic nervous system activity, and gene expression of neuropeptides involved in the regulation of energy balance. The primary role of leptin is to coordinate the responses of brain neuropeptide and neurotransmitter pathways to provide a situationally appropriate regulation of food intake, metabolic rate, energy balance, and fat storage (see Chapters 1 and 2).
Clinical studies of circulating leptin concentration have revealed the basic facts: Obese subjects have higher serum leptin concentrations than lean individuals, and concentrations increase with increasing percentage of body fat. Women have higher leptin concentrations than men, even when corrected for percentage of body fat. When obese subjects lose weight by caloric restriction, leptin concentrations decrease. Serum leptin concentrations in patients with eating disorders are appropriate for their percent body fat; that is, patients with anorexia nervosa have very low leptin levels, while overweight patients with bulimia nervosa have elevated leptin levels. Thus, the decreased food intake or failure to eat characteristic of anorexia nervosa is not a result of suppression of food intake by high leptin levels.
Fasting (18–24 hours) is followed by a decrease in leptin concentration by as much as 90% in humans. Thus, prolonged fasting leads to the coordinated inhibition of leptin production from groups of individual fat cells in many regions of the body. Refeeding af-