[HTML][HTML] Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease

KL Donnelly, CI Smith… - The Journal of …, 2005 - Am Soc Clin Investig
KL Donnelly, CI Smith, SJ Schwarzenberg, J Jessurun, MD Boldt, EJ Parks
The Journal of clinical investigation, 2005Am Soc Clin Investig
Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess
liver triacylglycerol (TAG), inflammation, and liver damage. The goal of the present study
was to directly quantify the biological sources of hepatic and plasma lipoprotein TAG in
NAFLD. Patients (5 male and 4 female; 44±10 years of age) scheduled for a medically
indicated liver biopsy were infused with and orally fed stable isotopes for 4 days to label and
track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the …
Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess liver triacylglycerol (TAG), inflammation, and liver damage. The goal of the present study was to directly quantify the biological sources of hepatic and plasma lipoprotein TAG in NAFLD. Patients (5 male and 4 female; 44±10 years of age) scheduled for a medically indicated liver biopsy were infused with and orally fed stable isotopes for 4 days to label and track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo lipogenesis (DNL) pathway, present in liver tissue and lipoprotein TAG. Hepatic and lipoprotein TAG fatty acids were analyzed by gas chromatography/mass spectrometry. NAFLD patients were obese, with fasting hypertriglyceridemia and hyperinsulinemia. Of the TAG accounted for in liver, 59.0%±9.9% of TAG arose from NEFAs; 26.1%±6.7%, from DNL; and 14.9%±7.0%, from the diet. The pattern of labeling in VLDL was similar to that in liver, and throughout the 4 days of labeling, the liver demonstrated reciprocal use of adipose and dietary fatty acids. DNL was elevated in the fasting state and demonstrated no diurnal variation. These quantitative metabolic data document that both elevated peripheral fatty acids and DNL contribute to the accumulation of hepatic and lipoprotein fat in NAFLD.
The Journal of Clinical Investigation