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Reduced hepatocyte fatty acid oxidation in outbred rats prescreened for susceptibility to diet-induced obesity

Abstract

Rats vary in their propensity to become obese when eating a high-fat diet, but the factors that make some rats susceptible and others resistant to diet-induced obesity are unclear. Recent studies show that rats predisposed to diet-induced obesity have a preexisting deficit in fat oxidation and suggest that this impairment is due in part to reduced fatty acid oxidation in liver. To determine directly whether rats susceptible to diet-induced obesity are less able to oxidize fatty acids in liver, we measured palmitate oxidation in hepatocytes isolated from outbred Sprague–Dawley rats that were identified while still eating a low-fat diet as obesity-prone or obesity-resistant by using a new screening procedure based on the change in plasma triglyceride concentration produced by an intragastric load of a fat and carbohydrate mixture. The results showed that hepatocytes from rats thus identified as obesity-prone oxidized 44% less palmitate in vitro than did those from obesity-resistant rats. This difference in hepatocyte fatty acid oxidation is consistent with and may explain at least in part the reduced capacity of obesity-prone rats to oxidize fat.

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Acknowledgements

This work was supported by NIH grant DK-53109. We thank Ms Lisa Outterbridge for her assistance with the experiments and Dr Michael Tordoff and Dr Danielle Reed for their comments on an earlier draft of the paper.

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Correspondence to M I Friedman.

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Ji, H., Friedman, M. Reduced hepatocyte fatty acid oxidation in outbred rats prescreened for susceptibility to diet-induced obesity. Int J Obes 32, 1331–1334 (2008). https://doi.org/10.1038/ijo.2008.71

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