Liver fat and lipid oxidation in humans
Article first published online: 7 JUL 2009
© 2009 John Wiley & Sons A/S
Volume 29, Issue 9, pages 1439–1446, October 2009
How to Cite
Kotronen, A., Seppälä-Lindroos, A., Vehkavaara, S., Bergholm, R., Frayn, K. N., Fielding, B. A. and Yki-Järvinen, H. (2009), Liver fat and lipid oxidation in humans. Liver International, 29: 1439–1446. doi: 10.1111/j.1478-3231.2009.02076.x
- Issue published online: 3 SEP 2009
- Article first published online: 7 JUL 2009
- Received 24 April 2009Accepted 2 June 2009
- carbohydrate oxidation;
- insulin resistance;
- lipid oxidation;
- liver fat
Background: Studies in animals show that changes in hepatic fatty acid oxidation alter liver fat content. Human data regarding whole-body and hepatic lipid oxidation are controversial and based on studies of only a few subjects.
Aims: We examined whether whole-body and hepatic lipid oxidation are altered in subjects with non-alcoholic fatty liver disease (NAFLD) compared with controls.
Methods: In vivo measurements of rates of substrate oxidation and insulin sensitivity (using the euglycaemic hyperinsulinaemic clamp technique in combination with indirect calorimetry and infusion of [3-3H]glucose) were performed in subjects with NAFLD [mean liver fat 14.0% (interquartile range 7.5–20.5%), n=29] and in control subjects [1.6% (1.0–3.0%), n=29]. Liver fat was measured using proton magnetic resonance spectroscopy. Plasma concentrations of 3-hydroxybutyrate (3-OHB) were measured as markers of hepatic lipid oxidation.
Results: In the basal state, substrate oxidation rates and serum 3-OHB concentrations were comparable in subjects with and without NAFLD. Plasma 3-OHB concentrations were similarly suppressed by insulin in both the groups. During the insulin infusion, whole-body lipid oxidation was inversely correlated with insulin-stimulated glucose disposal (r=−0.48, P<0.0001), which was lower in subjects with NAFLD [3.7±0.2 mg/(kg fat-free mass min)] than in the control subjects [5.0±0.3 mg/(kg fat-free mass min), P=0.0008].
Conclusions: Hepatic lipid oxidation is unchanged in NAFLD. Whole-body lipid oxidation is increased because of peripheral insulin resistance. These data imply that alterations in hepatic fatty acid oxidation do not contribute to liver fat content in humans.