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Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding

Abstract

AIMS/HYPOTHESIS: Metabolic disorders are commonly investigated using knockout and transgenic mouse models. A variety of mouse strains have been used for this purpose. However, mouse strains can differ in their inherent propensities to develop metabolic disease, which may affect the experimental outcomes of metabolic studies. We have investigated strain-dependent differences in the susceptibility to diet-induced obesity and insulin resistance in five commonly used inbred mouse strains (C57BL/6J, 129X1/SvJ, BALB/c, DBA/2 and FVB/N). METHODS: Mice were fed either a low-fat or a high-fat diet (HFD) for 8 weeks. Whole-body energy expenditure and body composition were then determined. Tissues were used to measure markers of mitochondrial metabolism, inflammation, oxidative stress and lipid accumulation. RESULTS: BL6, 129X1, DBA/2 and FVB/N mice were all susceptible to varying degrees to HFD-induced obesity, glucose intolerance and insulin resistance, but BALB/c mice exhibited some protection from these detrimental effects. This protection could not be explained by differences in mitochondrial metabolism or oxidative stress in liver or muscle, or inflammation in adipose tissue. Interestingly, in contrast with the other strains, BALB/c mice did not accumulate excess lipid (triacylglycerols and diacylglycerols) in the liver; this is potentially related to lower fatty acid uptake rather than differences in lipogenesis or lipid oxidation. CONCLUSIONS/INTERPRETATION: Collectively, our findings indicate that most mouse strains develop metabolic defects on an HFD. However, there are inherent differences between strains, and thus the genetic background needs to be considered carefully in metabolic studies.

Type Journal
Authors Montgomery, M. K.; Hallahan, N. L.; Brown, S. H.; Liu, M.; Mitchell, T. W.; Cooney, G. J.; Turner, N.
Responsible Garvan Author (missing name)
Publisher Name DIABETOLOGIA
Published Date 2013-05-01
Published Volume 56
Published Pages 1129-39
Status Published in-print
DOI 10.1007/s00125-013-2846-8
URL link to publisher's version http://www.ncbi.nlm.nih.gov/pubmed/23423668
OpenAccess link to author's accepted manuscript version https://publications.gimr.garvan.org.au/open-access/11535