Details

Autor(en) / Beteiligte

• Dubern, Beatrice
• Clement, Karine

Titel

Leptin and leptin receptor-related monogenic obesity

Ist Teil von

• Biochimie, 2012-10, Vol.94 (10), p.2111-2115

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2012

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• The studies based on candidate genes and encoded proteins known to cause severe obesity in rodents, have shown that these genes also contribute to human early-onset obesity especially for those involved in the leptin pathway: the leptin (LEP) and leptin receptor (LEPR) genes. Since 1997, less than 20 individuals carrying a LEP gene mutation have been identified. Patients are mostly characterized by severe early-onset obesity with severe hyperphagia and associated phenotype such hypogonadotrophic hypogonadism, high rate of infection associated with a deficiency in T cell and abnormalities of sympathetic nerve function. Therapeutic option (subcutaneous daily injection of leptin) is available for patients with LEP deficiency. It results in weight loss, mainly of fat mass, with a major effect on reducing food intake and on other dysfunctions including immunity and induction of puberty even in adults. In LEPR deficient subjects, phenotypic similarities with the LEP-deficient subjects were noticed, especially the exhibited rapid weight gain in the first few months of life, with severe hyperphagia and the endocrine abnormalities (hypogonadotrophic hypogonadism, insufficient somatotrophic or thyreotropic secretion). Leptin treatment is useless in the LEPR deficient subjects. Factors that could possibly bypass normal leptin delivery systems are being developed but are not yet currently available for the treatment of these patients. Measurement of circulating leptin may help for the diagnosis of such obesity: it is undetectable in LEP mutation carriers or extremely elevated in LEPR mutation carriers. Thus, LEPR gene screening might be also considered in subjects with the association of severe obesity with endocrine dysfunctions such as hypogonadism and with leptin related to corpulence level. ► Leptin and leptin receptor genes mutations are responsible for rare monogenic obesity. ► Patients are characterized by severe early-onset obesity with severe hyperphagia. ► Endocrine abnormalities such hypogonadotrophic hypogonadism are associated. ► Leptin treatment is available in leptin deficient patients resulting in weight loss. ► Measurement of circulating leptin may help for the diagnosis of such obesity.