Renne, Ulla, Langhammer, Martina, Brenmoehl, Julia, Walz, Christina, Zeissler, Anja, Tuchscherer, Armin, Piechotta, Marion, Wiesner, Rudolf J., Bielohuby, Maximilian ORCID: 0000-0002-9859-8156 and Hoeflich, Andreas ORCID: 0000-0003-2018-2836 (2013). Lifelong Obesity in a Polygenic Mouse Model Prevents Age- and Diet-Induced Glucose Intolerance- Obesity Is No Road to Late-Onset Diabetes in Mice. PLoS One, 8 (11). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Aims/Hypothesis: Visceral obesity holds a central position in the concept of the metabolic syndrome characterized by glucose intolerance in humans. However, until now it is unclear if obesity by itself is responsible for the development of glucose intolerance. Methods: We have used a novel polygenic mouse model characterized by genetically fixed obesity (DU6) and addressed age-and high fat diet-dependent glucose tolerance. Results: Phenotype selection over 146 generations increased body weight by about 2.7-fold in male 12-week DU6 mice (P<0.0001) if compared to unselected controls (Fzt:DU). Absolute epididymal fat mass was particularly responsive to weight selection and increased by more than 5-fold (P<0.0001) in male DU6 mice. At an age of 6 weeks DU6 mice consumed about twice as much food if compared to unselected controls (P<0.001). Absolute food consumption was higher at all time points measured in DU6 mice than in Fzt: DU mice. Between 6 and 12 weeks of age, absolute food intake was reduced by 15% in DU6 mice (P<0.001) but not in Fzt: DU mice. In both mouse lines feeding of the high fat diet elevated body mass if compared to the control diet (P<0.05). In contrast to controls, DU6 mice did not display high fat diet-induced increases of epididymal and renal fat. Control mice progressively developed glucose intolerance with advancing age and even more in response to the high fat diet. In contrast, obese DU6 mice did neither develop a glucose intolerant phenotype with progressive age nor when challenged with a high fat diet. Conclusions/Interpretation: Our results from a polygenic mouse model demonstrate that genetically pre-determined and life-long obesity is no precondition of glucose intolerance later in life.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Renne, UllaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langhammer, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenmoehl, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walz, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeissler, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tuchscherer, ArminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piechotta, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiesner, Rudolf J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bielohuby, MaximilianUNSPECIFIEDorcid.org/0000-0002-9859-8156UNSPECIFIED
Hoeflich, AndreasUNSPECIFIEDorcid.org/0000-0003-2018-2836UNSPECIFIED
URN: urn:nbn:de:hbz:38-471998
DOI: 10.1371/journal.pone.0079788
Journal or Publication Title: PLoS One
Volume: 8
Number: 11
Date: 2013
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LONG-TERM SELECTION; STRAIN FZT-DU; METABOLICALLY BENIGN; GENETIC-DETERMINANTS; ANIMAL-MODEL; GROWTH; LINES; FAT; MELLITUS; WEIGHTMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47199

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