db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet

To understand features of human obesity and type 2 diabetes mellitus (T2D) that can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style diet (WD) to weight-matched genetically obese leptin receptor-deficient mice (db/db). All mice were monitored for changes in body compositi...

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Main Authors: Susan J. Burke, Heidi M. Batdorf, David H. Burk, Robert C. Noland, Adrianna E. Eder, Matthew S. Boulos, Michael D. Karlstad, J. Jason Collier
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2017/8503754
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author Susan J. Burke
Heidi M. Batdorf
David H. Burk
Robert C. Noland
Adrianna E. Eder
Matthew S. Boulos
Michael D. Karlstad
J. Jason Collier
author_facet Susan J. Burke
Heidi M. Batdorf
David H. Burk
Robert C. Noland
Adrianna E. Eder
Matthew S. Boulos
Michael D. Karlstad
J. Jason Collier
author_sort Susan J. Burke
collection DOAJ
description To understand features of human obesity and type 2 diabetes mellitus (T2D) that can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style diet (WD) to weight-matched genetically obese leptin receptor-deficient mice (db/db). All mice were monitored for changes in body composition, glycemia, and total body mass. To objectively compare diet-induced and genetic models of obesity, tissue analyses were conducted using mice with similar body mass. We found that adipose tissue inflammation was present in both models of obesity. In addition, distinct alterations in metabolic flexibility were evident between WD-fed mice and db/db mice. Circulating insulin levels are elevated in each model of obesity, while glucagon was increased only in the db/db mice. Although both WD-fed and db/db mice exhibited adaptive increases in islet size, the db/db mice also displayed augmented islet expression of the dedifferentiation marker Aldh1a3 and reduced nuclear presence of the transcription factor Nkx6.1. Based on the collective results put forth herein, we conclude that db/db mice capture key features of human T2D that do not occur in WD-fed C57BL/6J mice of comparable body mass.
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spelling doaj-art-3e08a2ec6fbf4e98ae1c8e6e10aafd512025-08-20T03:55:41ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/85037548503754db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western DietSusan J. Burke0Heidi M. Batdorf1David H. Burk2Robert C. Noland3Adrianna E. Eder4Matthew S. Boulos5Michael D. Karlstad6J. Jason Collier7Laboratory of Immunogenetics, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USALaboratory of Islet Biology and Inflammation, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USACell Biology and Bioimaging Core Facility, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USASkeletal Muscle Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USADepartment of Surgery, Graduate School of Medicine, University of Tennessee Health Science Center, Knoxville, TN 37920, USADepartment of Surgery, Graduate School of Medicine, University of Tennessee Health Science Center, Knoxville, TN 37920, USADepartment of Surgery, Graduate School of Medicine, University of Tennessee Health Science Center, Knoxville, TN 37920, USALaboratory of Islet Biology and Inflammation, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USATo understand features of human obesity and type 2 diabetes mellitus (T2D) that can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style diet (WD) to weight-matched genetically obese leptin receptor-deficient mice (db/db). All mice were monitored for changes in body composition, glycemia, and total body mass. To objectively compare diet-induced and genetic models of obesity, tissue analyses were conducted using mice with similar body mass. We found that adipose tissue inflammation was present in both models of obesity. In addition, distinct alterations in metabolic flexibility were evident between WD-fed mice and db/db mice. Circulating insulin levels are elevated in each model of obesity, while glucagon was increased only in the db/db mice. Although both WD-fed and db/db mice exhibited adaptive increases in islet size, the db/db mice also displayed augmented islet expression of the dedifferentiation marker Aldh1a3 and reduced nuclear presence of the transcription factor Nkx6.1. Based on the collective results put forth herein, we conclude that db/db mice capture key features of human T2D that do not occur in WD-fed C57BL/6J mice of comparable body mass.http://dx.doi.org/10.1155/2017/8503754
spellingShingle Susan J. Burke
Heidi M. Batdorf
David H. Burk
Robert C. Noland
Adrianna E. Eder
Matthew S. Boulos
Michael D. Karlstad
J. Jason Collier
db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet
Journal of Diabetes Research
title db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet
title_full db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet
title_fullStr db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet
title_full_unstemmed db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet
title_short db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet
title_sort db db mice exhibit features of human type 2 diabetes that are not present in weight matched c57bl 6j mice fed a western diet
url http://dx.doi.org/10.1155/2017/8503754
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