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

Ilaria Croci, Nuala M. Byrne, Stéphane Choquette, Andrew P. Hills, Veronique S. Chachay, Andrew D. Clouston, Trisha M. O'Moore-Sullivan, Graeme A. Macdonald, Johannes B. Prins, Ingrid J. Hickman

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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.

Original languageEnglish
Pages (from-to)1625-1633
Number of pages9
JournalGut
Volume62
Issue number11
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

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Exercise
Liver
Hydroxybutyrates
Body Mass Index
Intra-Abdominal Fat
Insulin
Non-alcoholic Fatty Liver Disease
Indirect Calorimetry
Glucose Clamp Technique
Energy Metabolism
Histology
Fats
Tomography
Carbohydrates
Control Groups

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Croci, I., Byrne, N. M., Choquette, S., Hills, A. P., Chachay, V. S., Clouston, A. D., ... Hickman, I. J. (2013). Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease. Gut, 62(11), 1625-1633. https://doi.org/10.1136/gutjnl-2012-302789
Croci, Ilaria ; Byrne, Nuala M. ; Choquette, Stéphane ; Hills, Andrew P. ; Chachay, Veronique S. ; Clouston, Andrew D. ; O'Moore-Sullivan, Trisha M. ; Macdonald, Graeme A. ; Prins, Johannes B. ; Hickman, Ingrid J. / Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease. In: Gut. 2013 ; Vol. 62, No. 11. pp. 1625-1633.
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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.",
author = "Ilaria Croci and Byrne, {Nuala M.} and St{\'e}phane Choquette and Hills, {Andrew P.} and Chachay, {Veronique S.} and Clouston, {Andrew D.} and O'Moore-Sullivan, {Trisha M.} and Macdonald, {Graeme A.} and Prins, {Johannes B.} and Hickman, {Ingrid J.}",
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Croci, I, Byrne, NM, Choquette, S, Hills, AP, Chachay, VS, Clouston, AD, O'Moore-Sullivan, TM, Macdonald, GA, Prins, JB & Hickman, IJ 2013, 'Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease' Gut, vol. 62, no. 11, pp. 1625-1633. https://doi.org/10.1136/gutjnl-2012-302789

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 S.; Clouston, Andrew D.; O'Moore-Sullivan, Trisha M.; Macdonald, Graeme A.; Prins, Johannes B.; Hickman, Ingrid J.

In: Gut, Vol. 62, No. 11, 11.2013, p. 1625-1633.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Whole-body substrate metabolism is associated with disease severity in patients with non-alcoholic fatty liver disease

AU - Croci, Ilaria

AU - Byrne, Nuala M.

AU - Choquette, Stéphane

AU - Hills, Andrew P.

AU - Chachay, Veronique S.

AU - Clouston, Andrew D.

AU - O'Moore-Sullivan, Trisha M.

AU - Macdonald, Graeme A.

AU - Prins, Johannes B.

AU - Hickman, Ingrid J.

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

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U2 - 10.1136/gutjnl-2012-302789

DO - 10.1136/gutjnl-2012-302789

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JO - Gut

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SN - 0017-5749

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