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

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 1 H MRS measurement of total hepatic lipid with a novel ex vivo 2 H NMR analysis of HTG 2 H enrichment from 2 H‐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 1 H 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.