Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is frequently observed in insulin-resistant subjects and can lead to liver fibrosis and cirrhosis. The abnormalities of lipid metabolism behind this development of excess hepatic TG stores are poorly understood. Methods: To clarify these mechanisms we measured triglyceride secretion rate and the contributions of hepatic lipogenesis and reesterification of non-esterified fatty acids (NEFA) to this secretion in healthy subjects and in patients with clear evidence of NAFLD. All subjects were studied in the post-absorptive state. Hepatic lipogenesis was measured with deuterated water. NEFA turnover rate, triglyceride secretion rate and the contribution of NEFA reesterification to this secretion were determined with [1-C-13] palmitate infusion. Results: NAFLD patients had higher NEFA concentrations (p < 0.05) but normal NEFA turnover, rates (5.23 +/- 0.80 vs 5.91 +/- 0.97 mumol.lkg(-1).min(-1) in control subjects, ns). Despite a trend for higher plasma triglyceride levels in patients (p < 0.10), triglyceride turnover rates were not increased (0.11 +/- 0.01 mumol.kg(-1).min(-1) in patients vs 0.14 +/- 0.01 in controls, ns). However the contribution of hepatic lipogenesis to triglyceride secretion was largely increased in patients (14.9 +/- 2.7 vs 4.6 +/- 1.1 % p < 0.01) while that of NEFA reesterification was reduced (25.1 +/- 2.9 vs 52.8 +/- 6.2% p < 0.01). Conclusion: Enhanced lipogenesis appears as a major abnormality of hepatic fatty metabolism in subjects with NAFLD. Therapeutic measures aimed at decreasing hepatic lipogenesis would therefore be the most appropriate in order to reduce hepatic TG synthesis and content in such patients.