Lipid metabolism and substrate oxidation during intravenous fructose administration in cirrhosis.
We used isotope dilution techniques (constant intravenous [IV] infusion of 2-3H-glycerol and 1-14C-palmitate) and indirect calorimetry to measure lipid kinetics and substrate oxidation rates during IV fructose administration at 200 and then 500 mg/kg/h in eight cirrhotic patients and seven normal control subjects. Fasting plasma glucose, glycerol, and glycerol appearance rate (Ra) were similar in both groups, but insulin levels were fourfold higher in cirrhotics (P < .01). Fasting serum nonesterified fatty acid (NEFA) levels (cirrhotics, 869 +/- 124, controls, 717 +/- 90 mumol/L) and NEFA Ra (7.1 +/- 0.8 v 5.5 +/- 0.9 mumol/min/kg) were higher in cirrhotics, but the differences were not significant. Plasma fructose was similar in both groups at both fructose infusion rates. Fructose appeared to stimulate insulin secretion. With i.v. fructose, serum NEFA levels decreased, reaching similar low levels when 500 mg/kg/h was infused, due to a reduction in NEFA Ra and an increase in the NEFA metabolic clearance rate (MCR). Glycerol levels showed little change. As glycerol Ra decreased by less than 20% in both groups, the decrease in serum NEFA was primarily due to enhanced reesterification of fatty acids both within adipose tissue (preventing their release) and in other tissues (enhancing their removal from plasma). Although total fructose utilization was normal in cirrhotics, they oxidized more of the infused fructose; nonoxidative disposal was reduced (first step, 242 +/- 12 v 318 +/- 16 mg/kg in 2 hours, P < .002; second step, 657 +/- 32 v 786 +/- 21 mg/kg in 2 hours, P < .005). Although tissue fructose uptake is insulin-independent, insulin resistance in cirrhosis may influence the intracellular metabolism of fructose.
Kruszynska
Y T
YT
University Department of Medicine, Royal Free Hospital School of Medicine, London, UK.
Harry
D S
DS
Fryer
L G
LG
McIntyre
N
N
D000328:Adult; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005632:Fructose / Q000494:pharmacology*; D005990:Glycerol / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007700:Kinetics; D050356:Lipid Metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012016:Reference Values
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005632:Fructose; D005990:Glycerol