Modulation of muscle fuel metabolism in human volunteers by increasing the availability of muscle acetyl-CoA and carnitine moieties

This thesis investigated the impact of sodium acetate infusion on muscle fuel metabolism during low and high intensity exercise and demonstrated a decrease in fat oxidation during the former and a decrease in muscle lactate production during the latter. We propose that the rate of fat oxidation decreased during low intensity exercise due to acetate being preferentially metabolised over fat and possibly reduced muscle free carnitine availability. During high intensity exercise, muscle lactate accumulation decreased due to higher acetyl-CoA supply to the TCA cycle. This thesis also investigated the impact of chronic carnitine supplementation on overall glucose disposal and demonstrated a decrease in blood glucose and serum insulin concentrations following an OGTT in the carnitine group post-supplementation compared to baseline, coupled with a decrease in muscle 2-deoxyglucose accumulation in the carnitine group post-supplementation compared to control. We propose that carnitine-induced increased fat oxidation caused a decrease in hepatic fat deposition which in turn resulted in increasing glucose disposal by the liver. We also propose that increased hepatic glucose disposal resulted in reduced hepatic glucose release and hence diminished serum insulin concentrations. The impact of a chronic lifestyle intervention protocol involving either oral supplementation with carnitine (carnitine group) or placebo (control group) combined with carbohydrate and protein, together with regular exercise and a prescribed diet on muscle fuel metabolism and body composition in overweight volunteers was investigated in this thesis. This study demonstrated that increased muscle carnitine content caused an increase in fasting fat oxidation and a decrease in carbohydrate oxidation at rest. The carnitine group did not show any significant difference in body mass and body fat mass losses compared to the control group. Whether increased carnitine content, in combination with caloric restriction and exercise, has any impact on body composition seems likely but needs further investigations