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Original article
Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease
  1. Ilaria Croci1,
  2. Nuala M Byrne2,
  3. Stéphane Choquette3,
  4. Andrew P Hills4,5,
  5. Veronique S Chachay1,
  6. Andrew D Clouston6,
  7. Trisha M O'Moore-Sullivan4,7,
  8. Graeme A Macdonald6,8,
  9. Johannes B Prins1,4,
  10. Ingrid J Hickman1,4,9
  1. 1The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia
  2. 2Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
  3. 3Department of Physical Education and Sports, University of Sherbrooke, Sherbrooke, Canada
  4. 4Mater Medical Research Institute, Mater Mother's Hospital, Brisbane, Australia
  5. 5Griffith Health Institute, Griffith University, Brisbane, Australia
  6. 6School of Medicine, University of Queensland, Brisbane, Australia
  7. 7Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia
  8. 8Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia
  9. 9Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Australia
  1. Correspondence to Dr Ilaria Croci, The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Ipswich Road, Brisbane, 4102, QLD, Australia; ilaria.croci{at}uqconnect.edu.au

Abstract

Objectives 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/m2) and 15 healthy controls (BMI 23.4±2.7 kg/m2) were assessed. Respiratory quotient (RQ), whole-body fat (Fatox) and carbohydrate (CHOox) 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 Fatox). Severity of disease and steatosis were determined by liver histology, hepatic Fatox from plasma β-hydroxybutyrate concentrations, aerobic fitness expressed as Embedded Image , 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 Fatox 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 Fatox (1.2±0.3 vs 1.5±0.4 mg/kgFFM/min, p=0.024) and lower basal hepatic Fatox (ie, β-hydroxybutyrate, p=0.004). During exercise, they achieved lower maximal Fatox (2.5±1.4 vs. 5.8±3.7 mg/kgFFM/min, p=0.002) and lower Embedded Image (p<0.001) than controls. Fatox during exercise was not associated with disease severity (p=0.79).

Conclusions Overweight/obese patients with NAFLD had reduced hepatic Fatox and reduced whole-body Fatox 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.

  • Fatty Liver
  • Lipid Metabolism
  • Lipid Oxidation
  • Glucose Metabolism
  • Chronic Liver Disease

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