Sources of hepatic triglyceride accumulation during high-fat feeding in the healthy rat

Abstract

Hepatic triglyceride (HTG) accumulation from peripheral dietary sources and from endogenous de novo lipogenesis (DNL) was quantified in adult Sprague-Dawley rats by combining in vivo localized 1H MRS measurement of total hepatic lipid with a novel ex vivo 2H NMR analysis of HTG 2H enrichment from 2H-enriched body water. The methodology for DNL determination needs further validation against standard methodologies. To examine the effect of a high-fat diet on HTG concentrations and sources, animals (n = 5) were given high-fat chow for 35 days. HTG accumulation, measured by in vivo 1H MRS, increased significantly after 1 week (3.85 ± 0.60% vs 2.13 ± 0.34% for animals fed on a standard chow diet, P < 0.05) and was maintained until week 5 (3.30 ± 0.60% vs 1.12 ± 0.30%, P < 0.05). Animals fed on a high-fat diet were glucose intolerant (13.3 ± 1.3 vs 9.4 ± 0.8 mM in animals fed on a standard chow diet, for 60 min glycemia after glucose challenge, P < 0.05). In control animals, DNL accounted for 10.9 ± 1.0% of HTG, whereas in animals given the high-fat diet, the DNL contribution was significantly reduced to 1.0 ± 0.2% (P < 0.01 relative to controls). In a separate study to determine the response of HTG to weaning from a high-fat diet, animals with raised HTG (3.33 ± 0.51%) after 7days of a high-fat diet reverted to basal HTG concentrations (0.76 ± 0.06%) after an additional 7 days of weaning on a standard chow diet. These studies show that, in healthy rats, HTG concentrations are acutely influenced by dietary lipid concentrations. Although the DNL contribution to HTG content is suppressed by a high-fat diet in adult Sprague-Dawley rats, this effect is insufficient to prevent overall increases in HTG concentrations. Copyright © 2008 John Wiley & Sons, Ltd.