Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production
| Autor: | James D. Johnson, Gareth E. Lim, Shernaz X. Bamji, Nicole M. Templeman, Ali Asadi, José Diego Botezelli, Kwan-Yi Chu, G. Stefano Brigidi, Susanne M. Clee, Bradford G. Hoffman, Xiaoke Hu, Arya E. Mehran, Timothy J. Kieffer |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
endocrine system Pancreatic islet hyperplasia endocrine system diseases Physiology medicine.medical_treatment Adipose tissue 030209 endocrinology & metabolism White adipose tissue Carbohydrate metabolism Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Adipocyte medicine Hyperinsulinemia Molecular Biology 030304 developmental biology 2. Zero hunger 0303 health sciences Insulin nutritional and metabolic diseases Cell Biology medicine.disease Thermogenin Endocrinology chemistry |
| Zdroj: | Cell Metabolism. 16(6):723-737 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2012.10.019 |
| Popis: | Summary Hyperinsulinemia is associated with obesity and pancreatic islet hyperplasia, but whether insulin causes these phenomena or is a compensatory response has remained unsettled for decades. We examined the role of insulin hypersecretion in diet-induced obesity by varying the pancreas-specific Ins1 gene dosage in mice lacking Ins2 gene expression in the pancreas, thymus, and brain. Age-dependent increases in fasting insulin and β cell mass were absent in Ins1 +/− : Ins2 −/− mice fed a high-fat diet when compared to Ins1 +/+ : Ins2 −/− littermate controls. Remarkably, Ins1 +/− : Ins2 −/− mice were completely protected from diet-induced obesity. Genetic prevention of chronic hyperinsulinemia in this model reprogrammed white adipose tissue to express uncoupling protein 1 and increase energy expenditure. Normalization of adipocyte size and activation of energy expenditure genes in white adipose tissue was associated with reduced inflammation, reduced fatty acid spillover, and reduced hepatic steatosis. Thus, we provide genetic evidence that pathological circulating hyperinsulinemia drives diet-induced obesity and its complications. |
| Databáze: | OpenAIRE |
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