The Molecular Mechanisms of Fuel Utilization during Exercise.
Biology
Exercise is widely recognized for its positive impact on human health and well-being. The process of utilizing substrates in skeletal muscle during exercise is intricate and governed by complex mechanisms. Carbohydrates and lipids serve as the primary fuel sources for skeletal muscle during exercise. It is now understood that fuel selection during exercise is not solely determined by physical activity itself but is also influenced by the overall metabolic state of the body. The balance between lipid and carbohydrate utilization significantly affects exercise capacity, including endurance, fatigue, and overall performance. Therefore, comprehensively understanding the regulation of substrate utilization during exercise is of utmost importance. The aim of this review is to provide an extensive overview of the current knowledge regarding the pathways involved in the regulation of substrate utilization during exercise. By synthesizing existing research, we can gain a holistic perspective on the intricate relationship between exercise, metabolism, and fuel selection. This advanced understanding has the potential to drive advancements in the field of exercise science and contribute to the development of personalized exercise strategies for individuals looking to optimize their performance and overall health.
10.3390/biology12111450
Effects of insulin and exercise training on FGF21, its receptors and target genes in obesity and type 2 diabetes.
Kruse Rikke,Vienberg Sara G,Vind Birgitte F,Andersen Birgitte,Højlund Kurt
Diabetologia
AIMS/HYPOTHESIS:Pharmacological doses of FGF21 improve glucose tolerance, lipid metabolism and energy expenditure in rodents. Induced expression and secretion of FGF21 from muscle may increase browning of white adipose tissue (WAT) in a myokine-like manner. Recent studies have reported that insulin and exercise increase FGF21 in plasma. Obesity and type 2 diabetes are potentially FGF21-resistant states, but to what extent FGF21 responses to insulin and exercise training are preserved, and whether FGF21, its receptors and target genes are altered, remains to be established. METHODS:The effects of insulin during euglycaemic-hyperinsulinaemic clamps and 10 week endurance training on serum FGF21 were examined in individuals with type 2 diabetes and in glucose tolerant overweight/obese and lean individuals. Gene expression of FGF21, its receptors and target genes in muscle and WAT biopsies was evaluated by quantitative real-time PCR (qPCR). RESULTS:Insulin increased serum and muscle FGF21 independent of overweight/obesity or type 2 diabetes, and there were no effects associated with exercise training. The insulin-induced increases in serum FGF21 and muscle FGF21 expression correlated tightly (p < 0.001). In WAT, overweight/obesity with and without type 2 diabetes led to reduced expression of KLB, but increased FGFR1c expression. However, the expression of most FGF21 target genes was unaltered except for reduced CIDEA expression in individuals with type 2 diabetes. CONCLUSIONS/INTERPRETATION:Insulin-induced expression of muscle FGF21 correlates strongly with a rise in serum FGF21, and this response appears intact in overweight/obesity and type 2 diabetes. FGF21 resistance may involve reduced KLB expression in WAT. However, increased FGFR1c expression or other mechanisms seem to ensure adequate expression of most FGF21 target genes in WAT.
10.1007/s00125-017-4373-5
Fast and slow muscle fiber transcriptome dynamics with lifelong endurance exercise.
Journal of applied physiology (Bethesda, Md. : 1985)
We investigated fast and slow muscle fiber transcriptome exercise dynamics among three groups of men: lifelong exercisers (LLE, = 8, 74 ± 1 yr), old healthy nonexercisers (OH, = 9, 75 ± 1 yr), and young exercisers (YE, = 8, 25 ± 1 yr). On average, LLE had exercised ∼4 day·wk for ∼8 h·wk over 53 ± 2 years. Muscle biopsies were obtained pre- and 4 h postresistance exercise (3 × 10 knee extensions at 70% 1-RM). Fast and slow fiber size and function were assessed preexercise with fast and slow RNA-seq profiles examined pre- and postexercise. LLE fast fiber size was similar to OH, which was ∼30% smaller than YE ( < 0.05) with contractile function variables among groups, resulting in lower power in LLE ( < 0.05). LLE slow fibers were ∼30% larger and more powerful compared with YE and OH ( < 0.05). At the transcriptome level, fast fibers were more responsive to resistance exercise compared with slow fibers among all three cohorts ( < 0.05). Exercise induced a comprehensive biological response in fast fibers ( < 0.05) including transcription, signaling, skeletal muscle cell differentiation, and metabolism with vast differences among the groups. Fast fibers from YE exhibited a growth and metabolic signature, with LLE being primarily metabolic, and OH showing a strong stress-related response. In slow fibers, only LLE exhibited a biological response to exercise ( < 0.05), which was related to ketone and lipid metabolism. The divergent exercise transcriptome signatures provide novel insight into the molecular regulation in fast and slow fibers with age and exercise and suggest that the ∼5% weekly exercise time commitment of the lifelong exercisers provided a powerful investment for fast and slow muscle fiber metabolic health at the molecular level. This study provides the first insights into fast and slow muscle fiber transcriptome dynamics with lifelong endurance exercise. The fast fibers were more responsive to exercise with divergent transcriptome signatures among young exercisers (growth and metabolic), lifelong exercisers (metabolic), and old healthy nonexercisers (stress). Only lifelong exercisers had a biological response in slow fibers (metabolic). These data provide novel insights into fast and slow muscle fiber health at the molecular level with age and exercise.
10.1152/japplphysiol.00442.2023
Skeletal muscle energy metabolism in obesity.
Mengeste Abel M,Rustan Arild C,Lund Jenny
Obesity (Silver Spring, Md.)
Comparing energy metabolism in human skeletal muscle and primary skeletal muscle cells in obesity, while focusing on glucose and fatty acid metabolism, shows many common changes. Insulin-mediated glucose uptake in skeletal muscle and primary myotubes is decreased by obesity, whereas differences in basal glucose metabolism are inconsistent among studies. With respect to fatty acid metabolism, there is an increased uptake and storage of fatty acids and a reduced complete lipolysis, suggesting alterations in lipid turnover. In addition, fatty acid oxidation is decreased, probably at the level of complete oxidation, as -oxidation may be enhanced in obesity, which indicates mitochondrial dysfunction. Metabolic changes in skeletal muscle with obesity promote metabolic inflexibility, ectopic lipid accumulation, and formation of toxic lipid intermediates. Skeletal muscle also acts as an endocrine organ, secreting myokines that participate in interorgan cross talk. This review highlights interventions and some possible targets for treatment through action on skeletal muscle energy metabolism. Effects of exercise in vivo on obesity have been compared with simulation of endurance exercise in vitro on myotubes (electrical pulse stimulation). Possible pharmaceutical targets, including signaling pathways and drug candidates that could modify lipid storage and turnover or increase mitochondrial function or cellular energy expenditure through adaptive thermogenic mechanisms, are discussed.
10.1002/oby.23227
Chemerin affects blood lipid profile of high-fat diet male mice in sedentary and exercise states via glucose and lipid metabolism enzymes.
Endocrine connections
Adipokine chemerin plays important roles in disorders of glucose and lipid metabolism of obesity and obesity-related diseases, and exercise-induced improvement of glucose and lipid metabolism is closely related to the decrease of chemerin, but the mechanisms by which chemerin regulates glucose and lipid metabolism remain unclarified. Hypotestosterone induces male obesity and disorders of glucose and lipid metabolism through androgen receptor (AR) and its target genes: glucose and lipid metabolism-related molecules (including FOXO1, PEPCK, PGC-1α, and SCD1). Recently, the link between them has been reported that chemerin modulated the secretion of androgen. In this study, global chemerin knockout (chemerin (-/-)) mice were established to demonstrate the roles of chemerin in regulating blood glucose and blood lipid of mice under diet (high-fat (HFD) and normal diet) and exercise interventions and then to explore its mechanisms (AR - glucose and lipid metabolism enzymes). We found that the blood lipid and adipocyte size were low accompanied by the improvements in the levels of serum testosterone, gastrocnemius AR, and gastrocnemius FOXO1, SCD1, and PGC-1α in HFD chemerin (-/-) mice, but exercise-induced improvements of these indicators in HFD WT mice were attenuated or abolished in HFD chemerin (-/-) mice. In conclusion, the decrease of chemerin improved the blood lipid profile of HFD male mice at sedentary and exercise states, mediated partly by the increases of testosterone and AR to regulate glucose and lipid metabolism enzymes. To our knowledge, it is the first report that chemerin's regulation of glucose and lipid metabolism might be mediated by testosterone and AR in vivo.
10.1530/EC-23-0484
Impact of exercise training status on the fiber type-specific abundance of proteins regulating intramuscular lipid metabolism.
Shaw C S,Swinton C,Morales-Scholz M G,McRae N,Erftemeyer T,Aldous A,Murphy R M,Howlett K F
Journal of applied physiology (Bethesda, Md. : 1985)
Endurance training enhances the capacity for fat oxidation during exercise due to increased utilization of intramuscular lipid (IMCL). This study quantitatively investigated the impact of exercise training status on muscle fiber type-specific abundance of regulatory proteins involved in IMCL utilization. Endurance-trained [ = 7 subjects, peak oxygen consumption (V̇o) 62.6 ± 4.1 (SD) mL·min·kg] and non-endurance-trained ( = 8 subjects, V̇o 44.9 ± 5.3 mL·min·kg) young men completed an incremental exercise test to determine maximal fat oxidation (MFO) and maximal oxygen uptake. Fiber type-specific IMCL content and protein abundance were assessed with immunofluorescence microscopy and immunoblot analysis of pooled single muscle fibers and whole muscle. Endurance-trained individuals displayed a higher MFO rate (0.45 ± 0.15 vs. 0.19 ± 0.07 g/min, < 0.05), a greater proportion of type I muscle fibers, and higher IMCL content compared with untrained individuals ( < 0.05). Adipose triglyceride lipase, hormone-sensitive lipase, perilipin 2, perilipin 5, and hydroxyacyl-coenzyme A dehydrogenase abundances were ~2-3-fold higher in type I muscle fibers compared with type IIa fibers ( < 0.05). Correspondingly, these lipid proteins and oxidative enzymes were higher in endurance-trained individuals when assessed in whole muscle. MFO rate was strongly related to the proportion of type I fibers (= 0.81, < 0.01). The abundance of proteins involved in the regulation of IMCL storage and oxidation is highly muscle fiber type specific. The increased capacity for fat oxidation in endurance-trained individuals corresponded with increased IMCL content and elevated abundance of lipolytic and oxidative enzymes in combination with a greater proportion of type I muscle fibers. We have utilized contemporary techniques to compare the fiber type-specific characteristics of skeletal muscle from endurance-trained athletes and untrained individuals. We show that type I muscle fibers have a coordinated upregulation of proteins controlling intramuscular lipid storage, mobilization, and oxidation. Furthermore, the enhanced capacity for intramuscular lipid storage and utilization in endurance-trained individuals is related to the increased expression of lipid regulatory proteins combined with a greater proportion of type I muscle fibers.
10.1152/japplphysiol.00797.2019
Years of endurance exercise training remodel abdominal subcutaneous adipose tissue in adults with overweight or obesity.
Nature metabolism
Abnormalities in the structure and metabolic function of abdominal subcutaneous adipose tissue (aSAT) underlie many obesity-related health complications. Endurance exercise improves cardiometabolic health in adults with overweight or obesity, but the effects of endurance training on aSAT are unclear. We included male and female participants who were regular exercisers with overweight or obesity who exercised for >2 years, and cross-sectionally compared them with well-matched non-exercisers with overweight or obesity. Here we show aSAT from exercisers has a higher capillary density, lower Col6a abundance and fewer macrophages compared with non-exercisers. This is accompanied by a greater abundance of angiogenic, ribosomal, mitochondrial and lipogenic proteins. The abundance of phosphoproteins involved in protein translation, lipogenesis and direct regulation of transcripts is also greater in aSAT collected from exercisers. Exploratory ex vivo experiments demonstrate greater angiogenic capacity and higher lipid-storage capacity in samples cultured from aSAT collected from exercisers versus non-exercisers. Regular exercise may play a role in remodelling aSAT structure and proteomic profile in ways that may contribute to preserved cardiometabolic health.
10.1038/s42255-024-01103-x
Sustained Endurance Training Leads to Metabolomic Adaptation.
Metabolites
Endurance training induces several adaptations in substrate metabolism, especially in relation to glycogen conservation. The study aimed to investigate differences in the metabolism of lipids, lipid-like substances, and amino acids between highly trained and untrained subjects using targeted metabolomics. Depending on their maximum relative oxygen uptake (VO), subjects were categorized as either endurance-trained (ET) or untrained (UT). Resting blood was taken and plasma isolated. It was screened for changes of 345 metabolites, including amino acids and biogenic amines, acylcarnitines, glycerophosphocholines (GPCs), sphingolipids, hexoses, bile acids, and polyunsaturated fatty acids (PUFAs) by using liquid chromatography coupled to tandem mass spectrometry. Acylcarnitine (C14:1, down in ET) and five GPCs (lysoPC a C18:2, up in ET; PC aa C42:0, up in ET; PC ae C38:2, up in ET; PC aa C38:5, down in ET; lysoPC a C26:0, down in ET) were differently regulated in ET compared to UT. TCDCA was down-regulated in athletes, while for three ratios of bile acids CA/CDCA, CA/(GCA+TCA), and DCA/(GDCA+TDCA) an up-regulation was found. TXB2 and 5,6-EET were down-regulated in the ET group and 18S-HEPE, a PUFA, showed higher levels in 18S-HEPE in endurance-trained subjects. For PC ae C38:2, TCDCA, and the ratio of cholic acid to chenodeoxycholic acid, an association with VO was found. Numerous phospholipids, acylcarnitines, glycerophosphocholines, bile acids, and PUFAs are present in varying concentrations at rest in ET. These results might represent an adaptation of lipid metabolism and account for the lowered cardiovascular risk profile of endurance athletes.
10.3390/metabo12070658
Endurance Runners with Intramyocellular Lipid Accumulation and High Insulin Sensitivity Have Enhanced Expression of Genes Related to Lipid Metabolism in Muscle.
Kakehi Saori,Tamura Yoshifumi,Takeno Kageumi,Ikeda Shin-Ichi,Ogura Yuji,Saga Norio,Miyatsuka Takeshi,Naito Hisashi,Kawamori Ryuzo,Watada Hirotaka
Journal of clinical medicine
CONTEXT:Endurance-trained athletes have high oxidative capacities, enhanced insulin sensitivities, and high intracellular lipid accumulation in muscle. These characteristics are likely due to altered gene expression levels in muscle. DESIGN AND SETTING:We compared intramyocellular lipid (IMCL), insulin sensitivity, and gene expression levels of the muscle in eight nonobese healthy men (control group) and seven male endurance athletes (athlete group). Their IMCL levels were measured by proton-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR (qRT-PCR) and microarray analysis. RESULTS:IMCL levels in the tibialis anterior muscle were approximately 2.5 times higher in the athlete group compared to the control group, while the IMCL levels in the soleus muscle and GIR were comparable. In the microarray hierarchical clustering analysis, gene expression patterns were not clearly divided into control and athlete groups. In a gene set enrichment analysis with Gene Ontology gene sets, "RESPONSE TO LIPID" was significantly upregulated in the athlete group compared with the control group. Indeed, qRT-PCR analysis revealed that, compared to the control group, the athlete group had 2-3 times higher expressions of proliferator-activated receptor gamma coactivator-1 alpha (PGC1A), adiponectin receptors (AdipoRs), and fatty acid transporters including fatty acid transporter-1, plasma membrane-associated fatty acid binding protein, and lipoprotein lipase. CONCLUSIONS:Endurance runners with higher IMCL levels have higher expression levels of genes related to lipid metabolism such as PGC1A, AdipoRs, and fatty acid transporters in muscle.
10.3390/jcm9123951
Exercising your fat (metabolism) into shape: a muscle-centred view.
Gemmink Anne,Schrauwen Patrick,Hesselink Matthijs K C
Diabetologia
Fatty acids are an important energy source during exercise. Training status and substrate availability are determinants of the relative and absolute contribution of fatty acids and glucose to total energy expenditure. Endurance-trained athletes have a high oxidative capacity, while, in insulin-resistant individuals, fat oxidation is compromised. Fatty acids that are oxidised during exercise originate from the circulation (white adipose tissue lipolysis), as well as from lipolysis of intramyocellular lipid droplets. Moreover, hepatic fat may contribute to fat oxidation during exercise. Nowadays, it is clear that myocellular lipid droplets are dynamic organelles and that number, size, subcellular distribution, lipid droplet coat proteins and mitochondrial tethering of lipid droplets are determinants of fat oxidation during exercise. This review summarises recent insights into exercise-mediated changes in lipid metabolism and insulin sensitivity in relation to lipid droplet characteristics in human liver and muscle. Graphical abstract.
10.1007/s00125-020-05170-z
Reduced glucose tolerance and insulin sensitivity after prolonged exercise in endurance athletes.
Acta physiologica (Oxford, England)
AIM:The purpose of this study was to 1. investigate if glucose tolerance is affected after one acute bout of different types of exercise; 2. assess if potential differences between two exercise paradigms are related to changes in mitochondrial function; and 3. determine if endurance athletes differ from nonendurance-trained controls in their metabolic responses to the exercise paradigms. METHODS:Nine endurance athletes (END) and eight healthy nonendurance-trained controls (CON) were studied. Oral glucose tolerance tests (OGTT) and mitochondrial function were assessed on three occasions: in the morning, 14 h after an overnight fast without prior exercise (RE), as well as after 3 h of prolonged continuous exercise at 65% of VO max (PE) or 5 × 4 min at ~95% of VO max (HIIT) on a cycle ergometer. RESULTS:Glucose tolerance was markedly reduced in END after PE compared with RE. END also exhibited elevated fasting serum FFA and ketones levels, reduced insulin sensitivity and glucose oxidation, and increased fat oxidation during the OGTT. CON showed insignificant changes in glucose tolerance and the aforementioned measurements compared with RE. HIIT did not alter glucose tolerance in either group. Neither PE nor HIIT affected mitochondrial function in either group. END also exhibited increased activity of 3-hydroxyacyl-CoA dehydrogenase activity in muscle extracts vs. CON. CONCLUSION:Prolonged exercise reduces glucose tolerance and increases insulin resistance in endurance athletes the following day. These findings are associated with an increased lipid load, a high capacity to oxidize lipids, and increased fat oxidation.
10.1111/apha.13972
Exercise-induced BDNF promotes PPARδ-dependent reprogramming of lipid metabolism in skeletal muscle during exercise recovery.
Science signaling
Post-exercise recovery is essential to resolve metabolic perturbations and promote long-term cellular remodeling in response to exercise. Here, we report that muscle-generated brain-derived neurotrophic factor (BDNF) elicits post-exercise recovery and metabolic reprogramming in skeletal muscle. BDNF increased the post-exercise expression of the gene encoding PPARδ (peroxisome proliferator-activated receptor δ), a transcription factor that is a master regulator of lipid metabolism. After exercise, mice with muscle-specific knockout () exhibited impairments in PPARδ-regulated metabolic gene expression, decreased intramuscular lipid content, reduced β-oxidation, and dysregulated mitochondrial dynamics. Moreover, mice required a longer period to recover from a bout of exercise and did not show increases in exercise-induced endurance capacity. Feeding naïve mice with the bioavailable BDNF mimetic 7,8-dihydroxyflavone resulted in effects that mimicked exercise-induced adaptations, including improved exercise capacity. Together, our findings reveal that BDNF is an essential myokine for exercise-induced metabolic recovery and remodeling in skeletal muscle.
10.1126/scisignal.adh2783
RabGAPs in skeletal muscle function and exercise.
Espelage Lena,Al-Hasani Hadi,Chadt Alexandra
Journal of molecular endocrinology
The two closely related RabGAPs TBC1D1 and TBC1D4 are key signaling factors of skeletal muscle substrate utilization. In mice, deficiency in both RabGAPs leads to reduced skeletal muscle glucose transport in response to insulin and lower GLUT4 abundance. Conversely, Tbc1d1 and Tbc1d4 deficiency results in enhanced lipid use as fuel in skeletal muscle, through yet unknown mechanisms. In humans, variants in TBC1D1 and TBC1D4 are linked to obesity, insulin resistance and type 2 diabetes. While the specific function in metabolism of each of the two RabGAPs remains to be determined, TBC1D1 emerges to be controlling exercise endurance and physical capacity, whereas TBC1D4 may rather be responsible for maintaining muscle insulin sensitivity, muscle contraction, and exercise. There is growing evidence that TBC1D1 also plays an important role in skeletal muscle development, since it has been found to be associated to meat production traits in several livestock species. In addition, TBC1D1 protein abundance in skeletal muscle is regulated by both, insulin receptor and insulin-like growth factor-1 (IGF-1) receptor signaling. This review focuses on the specific roles of the two key signaling factors TBC1D1 and TBC1D4 in skeletal muscle metabolism, development and exercise physiology.
10.1530/JME-19-0143
Exercise-induced oxidative stress: Friend or foe?
Powers Scott K,Deminice Rafael,Ozdemir Mustafa,Yoshihara Toshinori,Bomkamp Matthew P,Hyatt Hayden
Journal of sport and health science
The first report demonstrating that prolonged endurance exercise promotes oxidative stress in humans was published more than 4 decades ago. Since this discovery, many ensuing investigations have corroborated the fact that muscular exercise increases the production of reactive oxygen species (ROS) and results in oxidative stress in numerous tissues including blood and skeletal muscles. Although several tissues may contribute to exercise-induced ROS production, it is predicted that muscular contractions stimulate ROS production in active muscle fibers and that skeletal muscle is a primary source of ROS production during exercise. This contraction-induced ROS generation is associated with (1) oxidant damage in several tissues (e.g., increased protein oxidation and lipid peroxidation), (2) accelerated muscle fatigue, and (3) activation of biochemical signaling pathways that contribute to exercise-induced adaptation in the contracting muscle fibers. While our understanding of exercise and oxidative stress has advanced rapidly during the last decades, questions remain about whether exercise-induced increases in ROS production are beneficial or harmful to health. This review addresses this issue by discussing the site(s) of oxidant production during exercise and detailing the health consequences of exercise-induced ROS production.
10.1016/j.jshs.2020.04.001
Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes.
Nature communications
Despite opposing insulin sensitivity and cardiometabolic risk, both athletes and patients with type 2 diabetes have increased skeletal myocyte fat storage: the so-called "athlete's paradox". In a parallel non-randomised, non-blinded trial (NCT03065140), we characterised and compared the skeletal myocyte lipid signature of 29 male endurance athletes and 30 patients with diabetes after undergoing deconditioning or endurance training respectively. The primary outcomes were to assess intramyocellular lipid storage of the vastus lateralis in both cohorts and the secondary outcomes were to examine saturated and unsaturated intramyocellular lipid pool turnover. We show that athletes have higher intramyocellular fat saturation with very high palmitate kinetics, which is attenuated by deconditioning. In contrast, type 2 diabetes patients have higher unsaturated intramyocellular fat and blunted palmitate and linoleate kinetics but after endurance training, all were realigned with those of deconditioned athletes. Improved basal insulin sensitivity was further associated with better serum cholesterol/triglycerides, glycaemic control, physical performance, enhanced post insulin receptor pathway signalling and metabolic sensing. We conclude that insulin-resistant, maladapted intramyocellular lipid storage and turnover in patients with type 2 diabetes show reversibility after endurance training through increased contributions of the saturated intramyocellular fatty acid pools. Clinical Trial Registration: NCT03065140: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity (MISTY).
10.1038/s41467-024-47843-y
Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers.
Burke Louise M,Ross Megan L,Garvican-Lewis Laura A,Welvaert Marijke,Heikura Ida A,Forbes Sara G,Mirtschin Joanne G,Cato Louise E,Strobel Nicki,Sharma Avish P,Hawley John A
The Journal of physiology
KEY POINTS:Three weeks of intensified training and mild energy deficit in elite race walkers increases peak aerobic capacity independent of dietary support. Adaptation to a ketogenic low carbohydrate, high fat (LCHF) diet markedly increases rates of whole-body fat oxidation during exercise in race walkers over a range of exercise intensities. The increased rates of fat oxidation result in reduced economy (increased oxygen demand for a given speed) at velocities that translate to real-life race performance in elite race walkers. In contrast to training with diets providing chronic or periodised high carbohydrate availability, adaptation to an LCHF diet impairs performance in elite endurance athletes despite a significant improvement in peak aerobic capacity. ABSTRACT:We investigated the effects of adaptation to a ketogenic low carbohydrate (CHO), high fat diet (LCHF) during 3 weeks of intensified training on metabolism and performance of world-class endurance athletes. We controlled three isoenergetic diets in elite race walkers: high CHO availability (g kg day : 8.6 CHO, 2.1 protein, 1.2 fat) consumed before, during and after training (HCHO, n = 9); identical macronutrient intake, periodised within or between days to alternate between low and high CHO availability (PCHO, n = 10); LCHF (< 50 g day CHO; 78% energy as fat; 2.1 g kg day protein; LCHF, n = 10). Post-intervention, V̇O2 peak during race walking increased in all groups (P < 0.001, 90% CI: 2.55, 5.20%). LCHF was associated with markedly increased rates of whole-body fat oxidation, attaining peak rates of 1.57 ± 0.32 g min during 2 h of walking at ∼80% V̇O2 peak . However, LCHF also increased the oxygen (O ) cost of race walking at velocities relevant to real-life race performance: O uptake (expressed as a percentage of new V̇O2 peak ) at a speed approximating 20 km race pace was reduced in HCHO and PCHO (90% CI: -7.047, -2.55 and -5.18, -0.86, respectively), but was maintained at pre-intervention levels in LCHF. HCHO and PCHO groups improved times for 10 km race walk: 6.6% (90% CI: 4.1, 9.1%) and 5.3% (3.4, 7.2%), with no improvement (-1.6% (-8.5, 5.3%)) for the LCHF group. In contrast to training with diets providing chronic or periodised high-CHO availability, and despite a significant improvement in V̇O2 peak , adaptation to the topical LCHF diet negated performance benefits in elite endurance athletes, in part due to reduced exercise economy.
10.1113/JP273230
Lipid metabolism during exercise.
Ranallo R F,Rhodes E C
Sports medicine (Auckland, N.Z.)
Fat is an extremely important substrate for muscle contraction, both at rest and during exercise. Triglycerides (TGs), stored in adipose tissue and within muscle fibres, are considered to be the main source of the free fatty acids (FFAs) oxidised during exercise. It is still unclear, however, how the use of these substrates is regulated during exercise. The regulation seems to be multifactorial and includes: (i) dietary and nutritional status; (ii) hormonal milieu; (iii) exercise mode, intensity and duration; and (iv) training status. On the other hand, the mechanism for FFA transport from its storage as triglycerides in adipose tissue and muscle to its place of utilisation in heart, skeletal muscle, kidney and liver is more clearly understood. It has been determined that the plasma FFA turnover rate is sufficiently rapid to account for most of the fat metabolised during low intensity exercise (25 to 40% VO2max). However, an exercise intensity of 65% VO2max results in a slight decrease in the amount of plasma FFA uptake by muscle tissue. Other studies have found that during prolonged exercise, muscle TGs become the predominant source of energy obtained from fat. Furthermore, it is widely documented that endurance activities increase the energy utilisation from fat while sparing carbohydrate sources. For example, during exercise on a cycle ergometer, nonplasma FFAs and plasma FFAs contribute 40%, and carbohydrates 60%, of the total calculated amount of energy expenditure before exercise and vice versa after exercise (60% nonplasma and plasma FFAs and 40% carbohydrates). Although it was many years before it was fully demonstrated, fat is now known to be transported in the blood as FFA bound to the protein carrier albumin. The mobilisation of FFA is primarily a function of sympathetic nervous activity directed towards the adipocytes, or the 'fat pad'. This nervous activity can be direct or may be an effect of circulating catecholamines such as adrenaline (epinephrine). This article summarises the role of fat metabolism during exercise.
10.2165/00007256-199826010-00003
Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals.
Sports medicine (Auckland, N.Z.)
BACKGROUND:Increased muscle mitochondrial mass is characteristic of elite professional endurance athletes (PAs), whereas increased blood lactate levels (lactatemia) at the same absolute submaximal exercise intensities and decreased mitochondrial oxidative capacity are characteristics of individuals with low aerobic power. In contrast to PAs, patients with metabolic syndrome (MtS) are characterized by a decreased capacity to oxidize lipids and by early transition from fat to carbohydrate oxidation (FATox/CHOox), as well as elevated blood lactate concentration [La] as exercise power output (PO) increases, a condition termed 'metabolic inflexibility'. OBJECTIVE:The aim of this study was to assess metabolic flexibility across populations with different metabolic characteristics. METHODS:We used indirect calorimetry and [La] measurements to study the metabolic responses to exercise in PAs, moderately active individuals (MAs), and MtS individuals. RESULTS:FATox was significantly higher in PAs than MAs and patients with MtS (p < 0.01), while [La] was significantly lower in PAs compared with MAs and patients with MtS. FATox and [La] were inversely correlated in all three groups (PA: r = -0.97, p < 0.01; MA: r = -0.98, p < 0.01; MtS: r = -0.92, p < 0.01). The correlation between FATox and [La] for all data points corresponding to all populations studied was r = -0.76 (p < 0.01). CONCLUSIONS:Blood lactate accumulation is negatively correlated with FATox and positively correlated with CHOox during exercise across populations with widely ranging metabolic capabilities. Because both lactate and fatty acids are mitochondrial substrates, we believe that measurements of [La] and FATox rate during exercise provide an indirect method to assess metabolic flexibility and oxidative capacity across individuals of widely different metabolic capabilities.
10.1007/s40279-017-0751-x
The Regulation of Fat Metabolism During Aerobic Exercise.
Muscella Antonella,Stefàno Erika,Lunetti Paola,Capobianco Loredana,Marsigliante Santo
Biomolecules
Since the lipid profile is altered by physical activity, the study of lipid metabolism is a remarkable element in understanding if and how physical activity affects the health of both professional athletes and sedentary subjects. Although not fully defined, it has become clear that resistance exercise uses fat as an energy source. The fatty acid oxidation rate is the result of the following processes: (a) triglycerides lipolysis, most abundant in fat adipocytes and intramuscular triacylglycerol (IMTG) stores, (b) fatty acid transport from blood plasma to muscle sarcoplasm, (c) availability and hydrolysis rate of intramuscular triglycerides, and (d) transport of fatty acids through the mitochondrial membrane. In this review, we report some studies concerning the relationship between exercise and the aforementioned processes also in light of hormonal controls and molecular regulations within fat and skeletal muscle cells.
10.3390/biom10121699
Applied physiology of marathon running.
Sjödin B,Svedenhag J
Sports medicine (Auckland, N.Z.)
Performance in marathon running is influenced by a variety of factors, most of which are of a physiological nature. Accordingly, the marathon runner must rely to a large extent on a high aerobic capacity. But great variations in maximal oxygen uptake (VO2 max) have been observed among runners with a similar performance capacity, indicating complementary factors are of importance for performance. The oxygen cost of running or the running economy (expressed, e.g. as VO2 15 at 15 km/h) as well as the fractional utilisation of VO2 max at marathon race pace (%VO2 Ma X VO2 max-1) [where Ma = mean marathon velocity] are additional factors which are known to affect the performance capacity. Together VO2 max, VO2 15 and %VO2 Ma X VO2 max-1 can almost entirely explain the variation in marathon performance. To a similar degree, these variables have also been found to explain the variations in the 'anaerobic threshold'. This factor, which is closely related to the metabolic response to increasing exercise intensities, is the single variable that has the highest predictive power for marathon performance. But a major limiting factor to marathon performance is probably the choice of fuels for the exercising muscles, which factor is related to the %VO2 Ma X VO2 max-1. Present indications are that marathon runners, compared with normal individuals, have a higher turnover rate in fat metabolism at given high exercise intensities expressed both in absolute (m/sec) and relative (%VO2 max) terms. The selection of fat for oxidation by the muscles is important since the stores of the most efficient fuel, the carbohydrates, are limited. The large amount of endurance training done by marathon runners is probably responsible for similar metabolic adaptations, which contribute to a delayed onset of fatigue and raise the VO2 Ma X VO2max-1. There is probably an upper limit in training kilometrage above which there are no improvements in the fractional utilisation of VO2 max at the marathon race pace. The influence of training on VO2 max and, to some extent, on the running economy appears, however, to be limited by genetic factors.
10.2165/00007256-198502020-00002
Lipid metabolism during endurance exercise.
Horowitz J F,Klein S
The American journal of clinical nutrition
Endogenous triacylglycerols represent an important source of fuel for endurance exercise. Triacylglycerol oxidation increases progressively during exercise; the specific rate is determined by energy requirements of working muscles, fatty acid delivery to muscle mitochondria, and the oxidation of other substrates. The catecholamine response to exercise increases lipolysis of adipose tissue triacylglycerols and, presumably, intramuscular triacylglycerols. In addition, increases in adipose tissue and muscle blood flow decrease fatty acid reesterification and facilitate the delivery of released fatty acids to skeletal muscle. Alterations in fatty acid mobilization and the relative use of adipose and intramuscular triacylglycerols during exercise depend, in large part, on degree of fitness and exercise intensity. Compared with untrained persons exercising at the same absolute intensity, persons who have undergone endurance training have greater fat oxidation during exercise without increased lipolysis. Available evidence suggests that the training-induced increase in fat oxidation is due primarily to increased oxidation of non-plasma-derived fatty acids, perhaps from intramuscular triacylglycerol stores. Fat oxidation is lower in high-intensity exercise than in moderate-intensity exercise, in part because of decreased fatty acid delivery to exercising muscles. Parenteral lipid supplementation during high-intensity exercise increases fat oxidation, but the effect of ingesting long-chain or medium-chain triacylglycerols on substrate metabolism during exercise is less clear. This review discusses the relation between fatty acid mobilization and oxidation during exercise and the effect of endurance training, exercise intensity, and lipid supplementation on these responses.
10.1093/ajcn/72.2.558S