title: Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity.
abstract: Obesity is the result of a long-term positive energy balance in which caloric intake overrides energy expenditure. This anabolic state results from the defective activity of hypothalamic neurons involved in the sensing and response to adiposity. However, it is currently unknown what the earliest obesity-linked hypothalamic defect is and how it orchestrates the energy imbalance present in obesity. Using an outbred model of diet-induced obesity we show that defective regulation of hypothalamic POMC is the earliest marker distinguishing obesity-prone from obesity-resistant mice. The early inhibition of hypothalamic POMC was sufficient to transform obesity-resistant in obesity-prone mice. In addition, the post-prandial change in the blood level of β-endorphin, a POMC-derived peptide, correlates with body mass gain in rodents and humans. Taken together, these results suggest that defective regulation of POMC expression, which leads to a change of β-endorphin levels, is the earliest hypothalamic defect leading to obesity.
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Gabriela F P
authors.initials: GF
authors.lastname: Souza
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Carina
authors.initials: C
authors.lastname: Solon
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Lucas F
authors.initials: LF
authors.lastname: Nascimento
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Jose C
authors.initials: JC
authors.lastname: De-Lima-Junior
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Nogueira
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Moura
authors.affiliation: Department of Internal Medicine, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Guilherme Z
authors.initials: GZ
authors.lastname: Rocha
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Milena
authors.initials: M
authors.lastname: Fioravante
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.|Faculty of Nursing, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bobbo
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Joseane
authors.initials: J
authors.lastname: Morari
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Razolli
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.|Faculty of Nursing, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Eliana P
authors.initials: EP
authors.lastname: Araujo
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, 13084-970 - Campinas-SP, Brazil.
authors.forename: Licio A
authors.initials: LA
authors.lastname: Velloso
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism; D002149:Energy Intake; D006801:Humans; D007031:Hypothalamus / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D055815:Young Adult; D001615:beta-Endorphin / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin