Dietary regulation of catabolic disposal of 4-hydroxynonenal analogs in rat liver

Our previous work in perfused rat livers has demonstrated that 4-hydroxynonenal (HNE) is catabolized predominantly via beta oxidation. Therefore, we hypothesized that perturbations in beta oxidation, such as diet-altered fatty acid oxidation activity, could lead to changes in HNE levels. To test our hypothesis, we (i) developed a simple and sensitive GC/MS method combined with mass isotopomer analysis to measure HNE and FINE analogs, 4-oxononenal (ONE) and 1,4-dihydroxynonene (DHN), and (ii) investigated the effects of four diets (standard, low-fat, ketogenic, and high-fat mix) on HNE, ONE, and DHN concentrations in rat livers. Our results showed that livers from rats fed the ketogenic diet or high-fat mix diet had high to omega-6 polyunsaturated fatty acid concentrations and markers of oxidative stress. However, high concentrations of HNE (1.6 +/- 0.5 nmol/g) and ONE (0.9 +/- 0.2 nmol/g) were found only in livers from rats fed the high-fat mix diet. Livers from rats fed the ketogenic diet had low HNE (0.8 +/- 0.1 nmol/g) and ONE (0.4 +/- 0.07 nmol/g), similar to rats fed the standard diet. A possible explanation is that the predominant pathway of FINE catabolism (i.e., beta oxidation) is activated in the liver by the ketogenic diet. This is consistent with a 10-fold decrease in malonyl-CoA in livers from rats fed a ketogenic diet compared to a standard diet. The accelerated catabolism of HNE lowers HNE and FINE analog concentrations in livers from rats fed the ketogenic diet. On the other hand, rats fed the high-fat mix diet had high rates of lipid synthesis and low rates of fatty acid oxidation, resulting in the slowing down of the catabolic disposal of HNE and HNE analogs. Thus, decreased HNE catabolism from a high-fat mix diet induces high concentrations of HNE and HNE analogs. The results of this work suggest a potential causal relationship to metabolic syndrome induced by Western diets (i.e., high-fat mix), as well as the effects of a ketogenic diet on the catabolism of lipid peroxidation products in liver. (C) 2011 Elsevier Inc. All rights reserved.