Liver fat and lipid oxidation in humans.
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.


OBJECTIVE
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-(3)H]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.
Kotronen
Anna
A
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland. anna.kotronen@helsinki.fi
Seppälä-Lindroos
Anneli
A
Vehkavaara
Satu
S
Bergholm
Robert
R
Frayn
Keith N
KN
Fielding
Barbara A
BA
Yki-Järvinen
Hannele
H
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000328:Adult; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020155:3-Hydroxybutyric Acid