Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease.
Level 4 - case-series / case-control
Small observational metabolic tracer study without a control group
PubMed 15864352 · doi:10.1172/JCI23621
What was done
Nine patients with nonalcoholic fatty liver disease (5 men, 4 women; mean age 44 ± 10 years) scheduled for a medically indicated liver biopsy were studied over 4 days. Participants received oral and intravenous stable isotope tracers to label and track three sources of liver and plasma lipoprotein triacylglycerol (TAG): serum nonesterified fatty acids (NEFAs), dietary fatty acids, and de novo lipogenesis (DNL). Fatty acids in liver biopsy tissue and lipoprotein TAG were measured using gas chromatography/mass spectrometry.
What was found
Patients were obese, with fasting hypertriglyceridemia and hyperinsulinemia. In liver tissue, 59.0% ± 9.9% of TAG originated from serum NEFAs, 26.1% ± 6.7% from DNL, and 14.9% ± 7.0% from the diet. The labeling pattern in VLDL was similar to that in the liver. Over the 4-day period, the liver demonstrated reciprocal use of adipose and dietary fatty acids, and DNL was elevated in the fasting state with no diurnal variation.
Why it matters
This study directly quantifies the human biological sources of liver fat in NAFLD, showing that peripheral adipose tissue lipolysis and unsuppressed de novo lipogenesis together account for the vast majority of hepatic triacylglycerol accumulation.
Limits
The study included only 9 participants and lacked a healthy control comparison group. Metabolic data were collected over a 4-day tracer protocol, and dietary intake was controlled but may not reflect long-term free-living dietary habits.