Does skeletal muscle carnitine availability influence fuel selection during exercise?

Abstract

24Fat and carbohydrate are the major fuel sources utilised for oxidative, mitochondrial 25 adenosine triphosphate (ATP) resynthesis during human skeletal muscle contraction. 26The relative contribution of these two substrates to ATP resynthesis and total energy 27 expenditure during exercise can vary substantially, and is predominantly determined 28 by fuel availability and exercise intensity and duration. For example, the increased 29 ATP demand that occurs with an increase in exercise intensity is met by increases in 30 both fat and carbohydrate oxidation up to an intensity of around 60 to 70% of 31 maximal oxygen consumption (VO2max). When exercise intensity increases beyond 32 this workload skeletal muscle carbohydrate utilisation is accelerated, which results in 33 a reduction and inhibition of the relative and absolute contribution of fat oxidation to 34 total energy expenditure. However, the precise mechanisms regulating muscle fuel 35 selection and underpinning the decline in fat oxidation remain unclear. This brief 36 review will primarily address the theory that a carbohydrate flux mediated reduction 37 in the availability of muscle carnitine to the mitochondrial enzyme carnitine 38 palmitoyltransferase 1 (CPT1), a rate limiting step in mitochondrial fat translocation, 39 is a key mechanism for the decline in fat oxidation during high intensity exercise. 40 This is discussed in relation to recent work in this area investigating fuel metabolism 41 at various exercise intensities and taking advantage of the discovery that skeletal 42 muscle carnitine content can be nutritionally increased in vivo in humans.

Resting skeletal muscle PNPLA2 (ATGL) and CPT1B are associated with peak fat oxidation rates in men and women but do not explain observed sex differences

“…RI, relative intensity & Kiens, 2012;Lundsgaard et al, 2018;Sahlin, 2009). The prevalent mechanism is believed to be via reduced free carnitine availability during intensive exercise, which inhibits the carnitine-palmitate transferase 1 (CPT1) reaction and the rate of entry of long-chain fatty acids into mitochondria (Lundsgaard et al, 2018;Stephens, 2018;Wall et al, 2011). Consistent with this, we found a moderate correlation between skeletal muscle CPT1B content and PFO rates.…”

An NMR-Based Approach to Identify Urinary Metabolites Associated with Acute Physical Exercise and Cardiorespiratory Fitness in Healthy Humans—Results of the KarMeN Study

“…To our knowledge, this is the first study reporting a post-exercise increase in the urinary excretion of carnitine (median FC = 1.68). Carnitine, which can either be synthesized from the amino acid lysine or ingested through diet, is largely stored in the skeletal muscle, where it is involved in the translocation of long-chain fatty acids into the mitochondrial matrix for subsequent β-oxidation and the buffering of accumulating acetyl-CoA [60]. Previous work has shown that acute exercise results in a higher muscle and plasma concentration of acetylcarnitines (reflecting an enhanced pyruvate and fatty acids oxidation) or long-chain acylcarnitines (reflecting an increased mobilization of free fatty acids) [24,[61][62][63][64], accompanied by a decrease in muscular [62,65] and blood [61,62] free carnitine.…”

A short-term intervention combining aerobic exercise with medium-chain triglycerides (MCT) is more ketogenic than either MCT or aerobic exercise alone: a comparison of normoglycemic and prediabetic older women

“…In fact, the entry of FFA into skeletal muscle requires carnitine before the FFA are ␤-oxidized and converted to ketones in mitochondria (Koeslag 1982). Muscle free carnitine availability is reduced during conditions of high glycolytic flux such as elevated carbohydrate availability, thus inhibiting long-chain fatty acid oxidation via the transporter carnitine palmitoyltransferase I (Stephens 2018).…”