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


Croci, I and Byrne, NM and Choquette, S and Hills, AP and Chachay, VS and Clouston, AD and O'Moore-Sullivan, T and Macdonald, GA and Prins, JB and Hickman, IJ, Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease, Gut, 62, (11) pp. 1625-1633. ISSN 0017-5749 (2013) [Refereed Article]

DOI: doi:10.1136/gutjnl-2012-302789


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 V·O2 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 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 V·O2 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 Fat ox 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.

Item Details

Item Type:Refereed Article
Keywords:chronic liver disease, fatty liver, glucose metabolism, lipid metabolism, lipid oxidation
Research Division:Health Sciences
Research Group:Health services and systems
Research Field:Health services and systems not elsewhere classified
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Public health (excl. specific population health) not elsewhere classified
UTAS Author:Byrne, NM (Professor Nuala Byrne)
UTAS Author:Hills, AP (Professor Andrew Hills)
ID Code:110668
Year Published:2013
Web of Science® Times Cited:57
Deposited By:Health Sciences
Deposited On:2016-08-09
Last Modified:2017-12-15

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