Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
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Exp. Clin. Endocrinol. Diabetes · Jan 1998
ReviewTo be lean or not to be lean. Is leptin the answer?
Leptin and the leptin receptor genes have been identified as the site of mutations in the peripheral adipocyte hormone pathway responsible for obesity in the ob/ob mouse (Zhang et al., 1994) and the db/db mouse (Chen et al., 1996). In obese humans, ob/ob like mutations in leptin are rare but confirm a role for leptin (Montague et al., 1997), and db/db like mutations in the leptin receptor have not been found (Considine et al., 1996a); however, the increased understanding of the molecular basis for obesity has generated tremendous interest among scientists and patients alike. The new knowledge could be the base for intelligent drugs for the treatment of obesity. Herein we will put in perspective a) the physiological background that led to the discovery of leptin, b) leptin biosynthesis, c) leptin action and d) the clinical issues related to leptin as a drug for the treatment of obesity.
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The high prevalence of obesity and its well documented association with the cardiovascular risk factors diabetes mellitus, dyslipidemia and hypertension represents a major problem for the general health status of industrialized societies. Although numerous studies have shown that genetic factors have a major influence on the regulation of energy homeostasis and the susceptibility to obesity, the genes and predisposing mutations involved are insufficiently understood. Among several known rodent models of obesity due to single gene mutations, mice homozygous for the obese (ob) gene exhibit massive early-onset obesity, hyperphagia, non-insulin-dependent diabetes mellitus, defective thermoregulation and infertility. ⋯ A mutation in the leptin receptor gene is responsible for the obese phenotype of db/db mice. Plasma leptin in humans is positively correlated with body fat mass, suggesting that leptin resistance rather than leptin deficiency is a common feature of human obesity. This review briefly summarizes the current status of the rapidly growing evidence that leptin plays an important role in the regulation of body weight and fat deposition.