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Dietary fat effects on hepatic lipid peroxidation and enzymes of H2O2 metabolism and NADPH Generation
Authors:Li-Chuan Chen  Gilbert Boissonneault  Michael G Hayek  Ching K Chow
Affiliation:(1) Graduate Center for Toxicology, University of Kentucky, 40506 Lexington, Kentucky;(2) Department of Clinical Sciences, University of Kentucky, 40506 Lexington, Kentucky;(3) Multidisciplinary Ph.D. Program in Nutritional Sciences, University of Kentucky, 40506 Lexington, Kentucky;(4) Department of Nutrition & Food Science, University of Kentucky, 212 Funkhouser Building, 40506-0054 Lexington, KY;(5) Present address: Differentiation Control Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Building 37 Room 3A-13, 20892 Bethesda, MD;(6) Present address: USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, 02111 Boston, MA
Abstract:The purpose of this study was to determine the effects of dietary fat quantity and fatty acid composition on hepatic H2O2-metabolizing systems, activities of NADPH-generating enzymes and lipid peroxidation. Onemonth-old male C57BL/6J mice were fed one of six diets: (i) 5% fat, rich in 18∶2n−6 fatty acid (5% N−6); (ii) 20% fat, rich in 18∶3n−3 (N−3); (iii) 20% fat, rich in 18∶2n−6 (N−6); (iv) 20% fat, rich in 18∶1n−9 (N−9); (v) 20% fat, rich in saturated fatty acids (SAT); and (vi) 20% fat, deficient in essential fatty acids (EFAD); for 11 wk. Comparisons between animal groups receiving different fat quantities showed that activities of glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) and malic enzyme (ME, EC 1.1.1.40) and the levels of conjugated dienes were significantly lower in the N−6 than in 5% N−6 group. Conversely, activities of catalase (CAT, EC 1.11.1.6) and seleniumglutathione peroxidase (SeGSHPx, EC 1.11.1.9) were higher in the N−6 than in 5% N−6 group. Among the five dietary groups receiving 20% fat but differing in fatty acid composition, CAT activity was lower in the N−9 group, SeGSHPx activity was lower in the EFAD group, and glutathione reductase (GSSGR, EC 1.6.4.2) activity was higher in the N−6 than in the N−3, N−9, SAT and EFAD groups. The EFAD group had much higher levels of total lipids and conjugated dienes, as well as activities of NADPH-generating enzymes, including G6PDH, ME and isocitrate dehydrogenase (EC 1.1.1.42), than the other four high-fat groups. The hepatic levels of malondialdehyde were not different among the five groups fed 20% fat. In the EFAD group, higher hepatic lipid content can be attributed to higher activities of NADPH-generating enzymes, and the elevation of conjugated diene levels may be related to increased oxygenation of 20∶−6 (Mead acid)via the lipoxygenase/cyclooxygenase pathway. In short, both dietary fat quantity and fatty acid composition selectively affected hepatic H2O2-metabolizing systems, activities of NADPH-generating enzymes and lipid peroxidation status.
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