Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease

Croci, Ilaria, Byrne, Nuala M., Choquette, Stéphane, Hills, Andrew P., Chachay, Veronique, Clouston, Andrew D., O'Moore-Sullivan, Trisha, MacDonald, Graeme A., Prins, Johannes, & Hickman, Ingrid (2013) Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease. Gut, 62(11), pp. 1625-1633.

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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.


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 , and visceral adipose tissue (VAT) measured by computed tomography.


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 (p<0.001) than controls. Fatox during exercise was not associated with disease severity (p=0.79).


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

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19 citations in Scopus
16 citations in Web of Science®
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ID Code: 54244
Item Type: Journal Article
Refereed: Yes
Keywords: non-alcoholic steatohepatitis, steatosis, fat oxidation, carbohydrate oxidation, exercise
DOI: 10.1136/gutjnl-2012-302789
ISSN: 0017-5749
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > PHYSIOLOGY (060600)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300) > Gastroenterology and Hepatology (110307)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > HUMAN MOVEMENT AND SPORTS SCIENCE (110600) > Exercise Physiology (110602)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Exercise & Nutrition Sciences
Copyright Owner: Copyright 2012 BMJ Publishing Group
Deposited On: 05 Nov 2012 00:33
Last Modified: 04 Dec 2013 03:16

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