Leptin and obesity.
Leptin, a protein containing 167 amino acids, demonstrates structural similarities with cytokine family and is mainly produced by adipocytes. The leptin receptor (OB-R) is a large membrane spanning protein that belongs to the gp 130 family of cytokine class I receptors. Besides the neuroendocrine effects of leptin in the control of food intake and energy expenditure, binding of this hormone has been proven in intestine, liver, kidney, skin, stomach, heart, spleen, lung, and so on. Thus leptin affects maternal, fetal and placental function, it appears to act as an endocrine and paracrine factor for the regulation of reproduction and puberty, prevents ectopic lipid deposition, modifies insulin sensitivity in the muscle or liver, and links the immune and endocrine systems. The LEP gene encodes for leptin. It has been localized in humans on the 7 alpha 31.3 chromosome and consists of three exons separated by two introns. In humans, a mutation in the LEP gene was reported in two children with the same cosanguineous pedigree. Other studies reported a polymorphism in the promoter untranslated exon 1 of the LEP gene (A19G), a polymorphism C(-188)A in the promoter region of the LEP gene (17) and a mutation at codon V110M. The biologic activities of leptin on target tissues are carried out through binding to a specific receptor, LEPR. LEPR maps in humans to the 1p31 chromosome. Variants commonly occur, which cause two nonconservative changes:lysine to asparagine at codon 656 (AAG to AAC) in exon 14 (K656N); lysine to arginine at codon 109 (AAG to AGG) in exon 4 (K109R); a nonconservative change glutamine to arginine at codon 223 (CAG to CGG); a silent TC change at codon 343; and a silent GA transition at codon 1019. Leptin is related with obesity and its metabolic disorders. However, new relation ships have been described; inflammatory bowel disease, cancer, bone formation, asthma and so on. In conclusion, despite the great advances in our knowledge of leptin physiology, many areas of investigation remain. Future research is expected to discover new molecules in the leptin pathway, to treat obesity and its related diseases.
de Luis
D A
DA
Institute of Endocrinology and Nutrition, Medical School and Unit of Investigation, Hospital Rio Hortega, University of Valladolid, Simancas, Valladolid, Spain. dadluis@yahoo.es
Perez Castrillón
J L
JL
Dueñas
A
A
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D024821:Metabolic Syndrome / Q000209:etiology; D051379:Mice; D009765:Obesity / Q000209:etiology* / Q000628:therapy; D054411:Receptors, Leptin / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D020738:Leptin; D054411:Receptors, Leptin