Artículo

Bumaschny, V.F.; Yamashita, M.; Casas-Cordero, R.; Otero-Corchón, V.; De Souza, F.S.J.; Rubinstein, M.; Low, M.J. "Obesity-programmed mice are rescued by early genetic intervention" (2012) Journal of Clinical Investigation. 122(11):4203-4212
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Abstract:

Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversible genetic mouse model of early-onset hyperphagia and severe obesity by selectively blocking the expression of the proopiomelanocortin gene (Pomc) in hypothalamic neurons. Eutopic reactivation of central POMC transmission at different stages of overweight progression normalized or greatly reduced food intake in these obesity-programmed mice. Hypothalamic Pomc rescue also attenuated comorbidities such as hyperglycemia, hyperinsulinemia, and hepatic steatosis and normalized locomotor activity. However, effectiveness of treatment to normalize body weight and adiposity declined progressively as the level of obesity at the time of Pomc induction increased. Thus, our study using a novel reversible monogenic obesity model reveals the critical importance of early intervention for the prevention of subsequent allostatic overload that auto-perpetuates obesity.

Registro:

Documento: Artículo
Título:Obesity-programmed mice are rescued by early genetic intervention
Autor:Bumaschny, V.F.; Yamashita, M.; Casas-Cordero, R.; Otero-Corchón, V.; De Souza, F.S.J.; Rubinstein, M.; Low, M.J.
Filiación:INGEBI-CONICET, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina
Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Department of Molecular and Integrative Physiology, University of Michigan, 6116 Brehm, 1000 Wall St., Ann Arbor, MI 48105, United States
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:proopiomelanocortin; tamoxifen; animal cell; animal experiment; animal model; article; attenuation; body weight; comorbidity; controlled study; disease severity; fatty liver; female; food intake; gene expression; gene targeting; gene therapy; hyperglycemia; hyperinsulinemia; hyperphagia; hypothalamus; locomotion; male; mouse; nerve cell; neurotransmission; nonhuman; obesity; priority journal; Adipose Tissue; Adiposity; Animals; Disease Models, Animal; Eating; Hyperphagia; Hypothalamus; Mice; Mice, Knockout; Neurons; Obesity; Pro-Opiomelanocortin
Año:2012
Volumen:122
Número:11
Página de inicio:4203
Página de fin:4212
DOI: http://dx.doi.org/10.1172/JCI62543
Título revista:Journal of Clinical Investigation
Título revista abreviado:J. Clin. Invest.
ISSN:00219738
CODEN:JCINA
CAS:proopiomelanocortin, 66796-54-1; tamoxifen, 10540-29-1; Pro-Opiomelanocortin, 66796-54-1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219738_v122_n11_p4203_Bumaschny

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Citas:

---------- APA ----------
Bumaschny, V.F., Yamashita, M., Casas-Cordero, R., Otero-Corchón, V., De Souza, F.S.J., Rubinstein, M. & Low, M.J. (2012) . Obesity-programmed mice are rescued by early genetic intervention. Journal of Clinical Investigation, 122(11), 4203-4212.
http://dx.doi.org/10.1172/JCI62543
---------- CHICAGO ----------
Bumaschny, V.F., Yamashita, M., Casas-Cordero, R., Otero-Corchón, V., De Souza, F.S.J., Rubinstein, M., et al. "Obesity-programmed mice are rescued by early genetic intervention" . Journal of Clinical Investigation 122, no. 11 (2012) : 4203-4212.
http://dx.doi.org/10.1172/JCI62543
---------- MLA ----------
Bumaschny, V.F., Yamashita, M., Casas-Cordero, R., Otero-Corchón, V., De Souza, F.S.J., Rubinstein, M., et al. "Obesity-programmed mice are rescued by early genetic intervention" . Journal of Clinical Investigation, vol. 122, no. 11, 2012, pp. 4203-4212.
http://dx.doi.org/10.1172/JCI62543
---------- VANCOUVER ----------
Bumaschny, V.F., Yamashita, M., Casas-Cordero, R., Otero-Corchón, V., De Souza, F.S.J., Rubinstein, M., et al. Obesity-programmed mice are rescued by early genetic intervention. J. Clin. Invest. 2012;122(11):4203-4212.
http://dx.doi.org/10.1172/JCI62543