Obesity-programmed mice are rescued by early genetic intervention
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 un...
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paper:paper_00219738_v122_n11_p4203_Bumaschny2023-06-08T14:44:51Z Obesity-programmed mice are rescued by early genetic intervention Otero Corchón, Verónica Rubinstein, Marcelo 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 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. Fil:Otero-Corchón, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219738_v122_n11_p4203_Bumaschny http://hdl.handle.net/20.500.12110/paper_00219738_v122_n11_p4203_Bumaschny |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Otero Corchón, Verónica Rubinstein, Marcelo Obesity-programmed mice are rescued by early genetic intervention |
| topic_facet |
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 |
| description |
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. |
| author |
Otero Corchón, Verónica Rubinstein, Marcelo |
| author_facet |
Otero Corchón, Verónica Rubinstein, Marcelo |
| author_sort |
Otero Corchón, Verónica |
| title |
Obesity-programmed mice are rescued by early genetic intervention |
| title_short |
Obesity-programmed mice are rescued by early genetic intervention |
| title_full |
Obesity-programmed mice are rescued by early genetic intervention |
| title_fullStr |
Obesity-programmed mice are rescued by early genetic intervention |
| title_full_unstemmed |
Obesity-programmed mice are rescued by early genetic intervention |
| title_sort |
obesity-programmed mice are rescued by early genetic intervention |
| publishDate |
2012 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219738_v122_n11_p4203_Bumaschny http://hdl.handle.net/20.500.12110/paper_00219738_v122_n11_p4203_Bumaschny |
| work_keys_str_mv |
AT oterocorchonveronica obesityprogrammedmicearerescuedbyearlygeneticintervention AT rubinsteinmarcelo obesityprogrammedmicearerescuedbyearlygeneticintervention |
| _version_ |
1768541690491043840 |