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bioRxiv · 10.1101/2022.10.26.513713

Limited Defense of Liver Energy Status in Rats Susceptible to Diet-induced Obesity

Friedman, M.·Ji, H.
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Abstract

Rats that are susceptible to diet-induced obesity have a preexisting reduced capacity for hepatic fatty acid oxidation compared with those resistant to diet-induced obesity. The eating response to administration of a fatty acid oxidation inhibitor is more closely associated with low liver energy status than it is with reduced hepatic fatty acid oxidation, a finding consistent with studies showing that lowered liver energy status stimulates food intake. To evaluate whether susceptibility to diet-induced obesity is associated with a preexisting impairment in liver energy status, we conducted two experiments in obesity-prone (OP) and -resistant (OR) outbred rats. In one experiment, OP rats increased food intake more than did OR rats during refeeding after a 24 h fast. When fasted and refed again, liver energy status (i.e., liver ATP content, ATP:ADP ratio and phosphorylation index) was lower in OP rats after a fast. When OP animals were refed fixed rations of food, liver energy status increased more slowly during refeeding than it did in OR rats. The delay in restoration of liver energy status during refeeding corresponded to the interval during which OP rats ate significantly more food in the intake test. In a second experiment, liver energy status was lower in OP than it was in OR rats after injection of the fructose analogue, 2,5-anhydro-D-mannitol, which depletes liver ATP. These results suggest that liver energy status is more vulnerable in rats susceptible to diet-induced obesity.

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Friedman, M., Ji, H.. 2022-10-27. Limited Defense of Liver Energy Status in Rats Susceptible to Diet-induced Obesity. https://doi.org/10.1101/2022.10.26.513713

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