Modeling leptin receptor insensitivity by comparing how leptin or leptin receptor mutations in mice affect body weight, basal metabolism, body temperature and feeding behaviors

摘要

Leptin, a protein hormone produced principally in adipose tissue, plays a major role in the regulation of food intake, hunger, satiety and metabolism. Most obesity is likely the result of the body’s resistance to leptin. The purpose of this experiment was to model leptin receptor insensitivity by comparing how the lack of leptin or the leptin receptor in mutant mice would affect body weight, basal metabolism, body temperature and feeding behaviors. Eighteen mice were used: 6 controls, 6 mutant ob/ob (defective for the expression of leptin), and 6 mutant db/db (defective for the expression of the leptin receptor). After 24 weeks of free access to food and water, the ob/ob mice weighed more than the control and db/db mice (P=0.0012). Both the ob/ob and db/db mice had lower metabolic rates (P = 0.0194) and body temperatures (P < 0.0001). As expected, the db/db mice had the greatest water intake (P=0.0060) and cage waste (P=0.0499) refl ective of their diabetic state. The normal mice ate more than the other mice, but the increases were not signifi cant; the ob/ob mice had much less food debris. These results indicate that mutations in the leptin protein or receptor interrupt normal metabolism in a manner similar to what may be experienced by individuals resistant to leptin. If a chronic intake of excessive calories results in increased adipose depositions, then over a lifetime, cell signaling activities may act to protect the leptin receptor from over bombardment by leptin, attenuate leptin’s regulatory function, and promote obesity.