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 7 days 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.
Delgado
T C
TC
Biochemistry Department, Coimbra University, Coimbra, Portugal.
Pinheiro
D
D
Caldeira
M
M
Castro
M M C A
MM
Geraldes
C F G C
CF
López-Larrubia
P
P
Cerdán
S
S
Jones
J G
JG
D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006262:Health; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism*; D014867:Water / Q000378:metabolism
D004041:Dietary Fats; D014280:Triglycerides; D014867:Water; D005947:Glucose