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Hyperinsulinemia drives diet-induced obesity independently of brain insulin production.
MedLine Citation:
PMID:  23217255     Owner:  NLM     Status:  In-Data-Review    
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.
Arya E Mehran; Nicole M Templeman; G Stefano Brigidi; Gareth E Lim; Kwan-Yi Chu; Xiaoke Hu; Jose Diego Botezelli; Ali Asadi; Bradford G Hoffman; Timothy J Kieffer; Shernaz X Bamji; Susanne M Clee; James D Johnson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell metabolism     Volume:  16     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  723-37     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
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