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

Croci, Ilaria, Byrne, Nuala M., Choquette, Stephane, Hills, Andrew P., Chachay, Veronique S., Clouston, Andrew D., O'Moore-Sullivan, Trisha M., Macdonald, Graeme A., Prins, Johannes B. and Hickman, Ingrid J. (2013) Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease. Gut, 62 11: 1625-1633. doi:10.1136/gutjnl-2012-302789

Author Croci, Ilaria
Byrne, Nuala M.
Choquette, Stephane
Hills, Andrew P.
Chachay, Veronique S.
Clouston, Andrew D.
O'Moore-Sullivan, Trisha M.
Macdonald, Graeme A.
Prins, Johannes B.
Hickman, Ingrid J.
Title Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease
Journal name Gut   Check publisher's open access policy
ISSN 0017-5749
Publication date 2013-11-01
Year available 2013
Sub-type Article (original research)
DOI 10.1136/gutjnl-2012-302789
Volume 62
Issue 11
Start page 1625
End page 1633
Total pages 9
Place of publication London, United Kingdom
Publisher B M J Group
Language eng
Formatted 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 V̇O 2 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 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 Fat ox (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 V̇O2 peak (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

Keyword Fatty Liver
Lipid Metabolism
Lipid Oxidation
Glucose Metabolism
Chronic Liver Disease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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