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

2005/05/02 by Kerry L. Donnelly, Coleman I. Smith, Sarah Jane Schwarzenberg +5 · 3,481 citations
Medicine · Nursing · #Adipose tissue #Biology #Biopsy #Cholesterol #Chylomicron #Diet, Metabolism, and Disease #Disease #Endocrinology #Fatty Acid Research and Health #Fatty liver #Hypertriglyceridemia #Internal medicine #Lipogenesis #Lipoprotein #Liver Disease Diagnosis and Treatment #Liver biopsy #Medicine #Nonalcoholic fatty liver disease #Triglyceride #Very low-density lipoprotein

paper · open access · doi:10.1172/jci23621

published in Journal of Clinical Investigation 115(5), 1343-1351 (American Society for Clinical Investigation)

openalex publication_date 2005/05/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04

Abstract

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.

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