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

Abstract

Objectives: In non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is intricately linked with a number of metabolic alterations. We studied substrate utilization in NAFLD during basal, insulin-stimulated and exercise conditions, and correlated these outcomes with disease severity.
Methods: 20 patients with NAFLD (BMI 34.16.7 kg/m2) and 15 healthy controls (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 (hyperinsulinemic-euglycemic clamp) and exercise (cycling at the intensity eliciting maximal Fatox). Severity of disease and steatosis was determined by liver histology; hepatic Fatox from plasma -hydroxybutyrate concentrations; aerobic fitness as ; visceral adipose tissue (VAT) by computed tomography.
Results: Within the overweight/obese NAFLD cohort, basal RQ was positively correlated 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 5 vs. <5 (P=.008). Both results were independent of VAT, %body fat and BMI. Compared to the lean control group, patients with NAFLD had lower basal whole-body Fatox (P=0.024) and lower basal hepatic Fatox (i.e -hydroxybutyrate, P=0.004). During exercise they achieved lower maximal Fatox (P=0.002) and lower (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 oxidize fat in basal conditions and histological features of NAFLD including severity of steatosis and NAFLD activity score.