title: Leptin resistance in obesity: An epigenetic landscape.
abstract: Leptin is an adipocyte-secreted hormone that inhibits food intake and stimulates energy expenditure through interactions with neuronal pathways in the brain, particularly pathways involving the hypothalamus. Intact functioning of the leptin route is required for body weight and energy homeostasis. Given its function, the discovery of leptin increased expectations for the treatment of obesity. However, most obese individuals and subjects with a predisposition to regain weight after losing it have leptin concentrations than lean individuals, but despite the anorexigenic function of this hormone, appetite is not effectively suppressed in these individuals. This phenomenon has been deemed leptin resistance and could be the result of impairments at a number of levels in the leptin signalling pathway, including reduced access of the hormone to its receptor due to changes in receptor expression or changes in post-receptor signal transduction. Epigenetic regulation of the leptin signalling circuit could be a potential mechanism of leptin function disturbance. This review discusses the molecular mechanisms, particularly the epigenetic regulation mechanisms, involved in leptin resistance associated with obesity and the therapeutic potential of these molecular mechanisms in the battle against the obesity pandemic.
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Crujeiras
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
authors.forename: Marcos C
authors.initials: MC
authors.lastname: Carreira
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Cabia
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Andrade
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Amil
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain. Electronic address: endocrine@usc.es.
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
mesh_terms: D044127:Epigenesis, Genetic; D006801:Humans; D020738:Leptin / Q000502:physiology* / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology*; D015398:Signal Transduction
chemical_list: D020738:Leptin
keywords: Appetite; DNA methylation; Leptin; Obesity pharmacotherapy