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Volume 6 Supplement 3

Metabolism, diet and disease

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Metabolic defects induced by high-fat feeding in mice are rapidly reversed by a low-fat diet


It is well established that high-fat feeding increases adiposity and impairs glucose metabolism in mice. The aim of this study was to determine the extent to which these changes are reversible if the high-fat diet (HFD) is removed.

Materials and methods

C57BI6 mice were fed a low-fat chow diet (LFD) or a HFD (45% calories as fat) for 9 weeks and body composition, glucose tolerance and tissue triglycerides were assessed. A group of fat-fed animals were then switched to a LFD (HFD-LFD) and after 4-5 days their body composition and glucose tolerance were reassessed.


Mice fed the HFD displayed a 73% increase (P<0.01) in whole-body fat mass, an 80% elevation (P<0.01) in muscle and liver triglyceride levels and a substantial impairment in glucose tolerance compared to animals fed the LFD (area under curve during GTT: 1166 ± 76 vs. 506 ± 47 mM.min, P<0.001). The switch to a LFD resulted in a transient decrease in total caloric intake, but only a small drop in body weight (31.3 ± 0.8 vs. 30.3 ± 0.5g, pre vs. post, P=0.06). Despite the minimal change in body weight, whole-body fat mass in the HFD-LFD group was reduced almost to the level of LFD controls (12.7% vs. 14.2% by DXA, LFD vs. HFD-LFD). Consistent with the reduction in whole-body adiposity, glucose tolerance (AUC during GTT: 510 ± 49 mM.min) and muscle and liver triglycerides in the HFD-LFD animals were also restored to the level of LFD animals. Intriguingly, a separate group of mice that were pair-fed HFD to match the drop in caloric intake in the HFD-LFD group, displayed no improvements in glucose tolerance or tissue triglyceride levels.


Our findings suggest that the metabolic defects induced by high-fat feeding in mice are rapidly reversible if animals are switched to a LFD.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Turner, N., Leslie, S.J., Hallahan, N.L. et al. Metabolic defects induced by high-fat feeding in mice are rapidly reversed by a low-fat diet. BMC Proc 6 (Suppl 3), P49 (2012).

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