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Liver fat and lipid oxidation in humans


Anna Kotronen, Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland, PO Box 700, Room C425B, FIN – 00029 HUCH, Helsinki, Finland Tel: +358 471 71991
Fax: +358 9 471 71896


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.