Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease.
OBJECTIVE
In non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is intricately linked with a number of metabolic alterations. We studied substrate utilisation in NAFLD during basal, insulin-stimulated and exercise conditions, and correlated these outcomes with disease severity.


METHODS
20 patients with NAFLD (mean ± SD body mass index (BMI) 34.1 ± 6.7 kg/m(2)) and 15 healthy controls (BMI 23.4 ± 2.7 kg/m(2)) were assessed. Respiratory quotient (RQ), whole-body fat (Fat ox) and carbohydrate (CHO ox) oxidation rates were determined by indirect calorimetry in three conditions: basal (resting and fasted), insulin-stimulated (hyperinsulinaemic-euglycaemic clamp) and exercise (cycling at an intensity to elicit maximal Fat ox). Severity of disease and steatosis were determined by liver histology, hepatic Fat ox from plasma β-hydroxybutyrate concentrations, aerobic fitness expressed as VO2 peak, and visceral adipose tissue (VAT) measured by computed tomography.


RESULTS
Within the overweight/obese NAFLD cohort, basal RQ correlated positively with steatosis (r=0.57, p=0.01) and was higher (indicating smaller contribution of Fat ox to energy expenditure) in patients with NAFLD activity score (NAS) ≥ 5 vs <5 (p=0.008). Both results were independent of VAT, % body fat and BMI. Compared with the lean control group, patients with NAFLD had lower basal whole-body Fat ox (1.2 ± 0.3 vs 1.5 ± 0.4 mg/kg FFM/min, p=0.024) and lower basal hepatic Fat ox (ie, β-hydroxybutyrate, p=0.004). During exercise, they achieved lower maximal Fat ox (2.5 ± 1.4 vs. 5.8 ± 3.7 mg/kg FFM/min, p=0.002) and lower VO2 peak (p<0.001) than controls. Fat ox during exercise was not associated with disease severity (p=0.79).


CONCLUSIONS
Overweight/obese patients with NAFLD had reduced hepatic Fat ox and reduced whole-body Fat ox under basal and exercise conditions. There was an inverse relationship between ability to oxidise fat in basal conditions and histological features of NAFLD including severity of steatosis and NAS.
The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.
Ilaria
I
Croci
Nuala M
NM
Byrne
Stéphane
S
Choquette
Andrew P
AP
Hills
Veronique S
VS
Chachay
Andrew D
AD
Clouston
Trisha M
TM
O'Moore-Sullivan
Graeme A
GA
Macdonald
Johannes B
JB
Prins
Ingrid J
IJ
Hickman
D000328:Adult; D001481:Basal Metabolism / Q000502:physiology; D002153:Calorimetry, Indirect / Q000379:methods; D016022:Case-Control Studies; D004734:Energy Metabolism / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D005080:Exercise Test / Q000379:methods; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000378:metabolism; D050177:Overweight / Q000150:complications / Q000378:metabolism; D010084:Oxidation-Reduction; D012720:Severity of Illness Index; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides