Gluconeogenesis during endurance exercise in cyclists habituated to a long‐term low carbohydrate high‐fat diet

Abstract

Key pointsr Blood glucose is an important fuel for endurance exercise. It can be derived from ingested carbohydrate, stored liver glycogen and newly synthesized glucose (gluconeogenesis).r We hypothesized that athletes habitually following a low carbohydrate high fat (LCHF) diet would have higher rates of gluconeogenesis during exercise compared to those who follow a mixed macronutrient diet.r We used stable isotope tracers to study glucose production kinetics during a 2 h ride in cyclists habituated to either a LCHF or mixed macronutrient diet.r The LCHF cyclists had lower rates of total glucose production and hepatic glycogenolysis but similar rates of gluconeogenesis compared to those on the mixed diet.r The LCHF cyclists did not compensate for reduced dietary carbohydrate availability by increasing glucose synthesis during exercise but rather adapted by altering whole body substrate utilization.Abstract Endogenous glucose production (EGP) occurs via hepatic glycogenolysis (GLY) and gluconeogenesis (GNG) and plays an important role in maintaining euglycaemia. Rates of GLY and GNG increase during exercise in athletes following a mixed macronutrient diet; however, these processes have not been investigated in athletes following a low carbohydrate high fat (LCHF) diet. Therefore, we studied seven well-trained male cyclists that were habituated to either a LCHF (7% carbohydrate, 72% fat, 21% protein) or a mixed diet (51% carbohydrate, 33% fat, 16% protein) for longer than 8 months. After an overnight fast, participants performed a 2 h laboratory ride at 72% of maximal oxygen consumption. Glucose kinetics were measured at rest and during the final 30 min of exercise by infusion of [6,6-2 H 2 ]-glucose and the ingestion of 2 H 2 O tracers. Rates of EGP and GLY both at rest and during exercise were significantly lower in the LCHF group than the mixed diet group (Exercise EGP: LCHF, 6.0 ± 0.9 mg kg −1 min −1 , Mixed, 7.8 ± 1.1 mg kg −1 min −1 , P < 0.01; Exercise GLY: LCHF, 3.2 ± 0.7 mg kg −1 min −1 , Mixed, 5.3 ± 0.9 mg kg −1 min −1 , P < 0.01). Conversely, no difference was detected in rates of GNG between groups at rest or during exercise (Exercise: LCHF, 2.8 ± 0.4 mg kg −1 min −1 , Mixed, 2.5 ± 0.3 mg kg −1 min −1 , P = 0.15). We conclude that athletes on a LCHF diet do not compensate for reduced glucose availability via higher rates of glucose synthesis compared to athletes on a mixed diet. Instead, GNG remains relatively stable, whereas glucose oxidation and GLY are influenced by dietary factors. Abbreviations ASA24, automated self-administered 24 h recall; βHB, β-hydroxybutyrate; BMI, body mass index; CV, coefficient of variation; EGP, endogenous glucose production; FFA, free fatty acids; GLY, glycogenolysis; GNG, gluconeogenesis; HR, heart rate; HR max , maximum heart rate; LCHF, low carbohydrate high fat; MIDA, mass isotopomer distribution analysis; MUFA, monounsaturated fatty acids; PPO, peak power output; PUFA, polyunsaturated fatty acids; R a , rate of appearance; R d , rate of disappearance; RER, respira...

Dietary intake is independently associated with the maximal capacity for fat oxidation during exercise,

“…An increase of glycolytic flux during exercise (e.g., with high exercise intensities or increased carbohydrate provision) can also directly downregulate mitochondrial long-chain FAT-OX (35, 36). The positive association of fat intake with the MFO was also consistent with previous studies in which high-fat or ketogenic diets substantially augmented FAT-OX or the MFO (12, 15, 18, 37–39). Fat intake has been suggested to influence FAT-OX through several mechanisms including greater plasma and intramuscular lipid availability (40, 41), greater expression of key proteins that are involved in cellular fatty acid uptake (37, 38, 42) and β oxidation (37, 43), and the reciprocal downregulation of enzymes (e.g., pyruvate dehydrogenase) that are involved in carbohydrate oxidation (44–46).…”

Evidence that supports the prescription of low-carbohydrate high-fat diets: a narrative review

“…LCHF diets increase reliance on fat oxidation for energy production, especially during exercise,53 54 as shown by increased blood ketone concentrations and with reductions in respiratory quotient and blood insulin concentrations 53–55. This state of increased lipolysis with reduced lipogenesis contributes to a metabolic milieu theoretically favouring fat loss.…”

“…While the latter is life-threatening, nutritional ketosis is a normal physiological response to dietary carbohydrate restriction, in which the body alters its primary fuel utilisation from carbohydrates to fat. This change spares blood glucose for use particularly by the brain which has an obligatory glucose requirement of about 25 g/day,96 when using alternative fuels including ketones or lactate in fat-adapted persons 54. Carbohydrate restriction increases the production of ketone bodies (acetoacetate, β-hydroxybuterate and acetone) by the liver 97.…”

Muscle molecular adaptations to endurance exercise training are conditioned by glycogen availability: a proteomics‐based analysis in the McArdle mouse model

“…), or delayed liver glycogenolysis (Webster et al . ). Elucidating the muscle metabolic adaptations to endurance exercise training as a function of glycogen availability is of interest as it may help to gain insight into the mechanisms that mediate the muscle adaptations to this type of training.…”

“…protein 53 (p53), peroxisome proliferator-activated receptor delta (PPARδ)) and transcriptional co-activators (e.g. peroxisome proliferator-activated receptor-1α (PGC-1α)) (Bartlett et al 2015), increased fat oxidation (Lane et al 2015), or delayed liver glycogenolysis (Webster et al 2016). Elucidating the muscle metabolic adaptations to endurance exercise training as a function of glycogen availability is of interest as it may help to gain insight into the mechanisms that mediate the muscle adaptations to this type of training.…”