Hepatocyte p53 ablation induces metabolic dysregulation that is corrected by food restriction and vertical sleeve gastrectomy in mice
| Autor: | Darline Garibay, Seon A. Lee, Erin K. Daugherity, Elizabeth S. Moore, Mridusmita Saikia, Robert S. Weiss, Paul Cohen, Marlena M. Holter, Kathleen Kelly, Anne K. McGavigan, Lily Ngyuen, Bethany P. Cummings |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Blood Glucose Male medicine.medical_specialty Sleeve gastrectomy medicine.medical_treatment Biology Diet High-Fat Weight Gain Biochemistry Article Pathogenesis 03 medical and health sciences Eating Mice 0302 clinical medicine Metabolic Diseases Gastrectomy Internal medicine Diabetes mellitus parasitic diseases Weight Loss Genetics medicine Glucose homeostasis Animals Homeostasis Obesity Molecular Biology Caloric Restriction Mice Knockout Body Weight medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure Food Hepatocyte Knockout mouse Hepatocytes medicine.symptom Tumor Suppressor Protein p53 Energy Metabolism Weight gain 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | FASEB J |
| Popis: | P53 has been implicated in the pathogenesis of obesity and diabetes; however, the mechanisms and tissue sites of action are incompletely defined. Therefore, we investigated the role of hepatocyte p53 in metabolic homeostasis using a hepatocyte-specific p53 knockout mouse model. To gain further mechanistic insight, we studied mice under two complementary conditions of restricted weight gain: vertical sleeve gastrectomy (VSG) or food restriction. VSG or sham surgery was performed in high-fat diet-fed male hepatocyte-specific p53 wild-type and knockout littermates. Sham-operated mice were fed ad libitum or food restricted to match their body weight to VSG-operated mice. Hepatocyte-specific p53 ablation in sham-operated ad libitum-fed mice impaired glucose homeostasis, increased body weight, and decreased energy expenditure without changing food intake. The metabolic deficits induced by hepatocyte-specific p53 ablation were corrected, in part by food restriction, and completely by VSG. Unlike food restriction, VSG corrected the effect of hepatocyte p53 ablation to lower energy expenditure, resulting in a greater improvement in glucose homeostasis compared with food restricted mice. These data reveal an important new role for hepatocyte p53 in the regulation of energy expenditure and body weight and suggest that VSG can improve alterations in energetics associated with p53 dysregulation. |
| Databáze: | OpenAIRE |
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