Hepatic mitochondrial function (HMF) assessed by the ¹³ C-ketoisocaproate breath test ( ¹³ C-KICA BT) has been previously shown to be significantly associated with the severity of biopsy proven non-alcoholic fatty liver disease (NAFLD). However, it is uncertain whether any perturbation in HMF relates specifically to severity of liver disease or factors associated with metabolic syndrome within (NAFLD). Our aim was to investigate whether there was any change in HMF assessed by ¹³ C-KICA BT in patients with NAFLD compared to control subjects, and to assess the factors that are independently associated with HMF. Methods . 77 patients with NAFLD and 11 healthy control subjects were studied. HMF was assessed using ¹³ C-KICA BT and expressed as cumulative % ¹³ C-dose recovered on breath over 1 h (cPDR over 1 h). Liver fat and fibrosis was assessed by transient elastography. Multivariable linear regression modelling was undertaken to test the independence of associations with HMF. Results. HMF (cPDR over 1 h) was lower in NAFLD compared to controls [13.4% (4.8) v. 21.0% (6.3); p < 0.0001)]. In NAFLD, HMF was lower in patients with diabetes versus no diabetes [12.7% (3.4) v. 14.3% (6.1); p = 0.003)]. Regression modelling showed age ( β = −0.08; p = 0.01), waist circumference ( β = −0.08; p = 0.01), hip circumference ( β = −0.04; p = 0.01), aspartate aminotransferase (AST) ( β = −0.05; p = 0.01) and diabetes status ( β = −1.81; p = 0.01) were independently associated with HMF (R ² = 41.5%; p < 0.0001). Conclusions. In patients with NAFLD (compared to healthy subjects), there was a reduction in HMF assessed by the ¹³ C-KICA BT. Furthermore, in patients with NAFLD, HMF is independent and inversely associated with age, waist and hip circumference, AST and diabetes status.

It is unclear whether the rate of weight loss, independent of magnitude, affects whole body protein metabolism and the synthesis and plasma concentrations of specific hepatic secretory proteins. We examined 1 ) whether lean men losing weight rapidly (starvation) show greater changes in whole body protein kinetics, synthesis, and circulating concentrations of selected hepatic secretory proteins than those losing the same amount of weight more slowly [very low energy diet (VLED)]; and 2 ) whether plasma concentrations and synthetic rates of these proteins are related. Whole body protein kinetics were measured using [1-13C]leucine in 11 lean men (6 starvation, 5 VLED). Fractional and absolute synthetic rates of HDL-apolipoprotein A1 (apoA1), retinol binding protein, transthyretin, α1-antitrypsin (α1-AT), and transferrin were measured using a prime-constant intravenous infusion of [13C2]glycine. Compared with VLED group, the starvation group showed greater increases (at a 5% weight loss) in whole body protein oxidation ( P < 0.05); fractional synthetic rates of HDL-apoA1 (25.3 vs. −1.52%; P = 0.003) and retinol binding protein (30.6 vs. 7.1%; P = 0.007); absolute synthetic rates of HDL-apoA1 (7.1 vs. −3.8 mg·kg−1·day−1; P = 0.003) and α1-AT (17.8 vs. 3.6 mg·kg−1·day−1; P = 0.02); and plasma concentration of α1-AT ( P = 0.025). Relationships between synthetic rates and plasma concentrations varied between the secreted proteins. It is concluded that synthetic rates of hepatic secreted proteins in lean men are more closely related to the rate than the magnitude of weight loss. Changes in concentration of these secreted proteins can occur independently of changes in synthetic rates, and vice versa.