The Molecular Mechanisms of Fuel Utilization during Exercise
Abstract
:Simple Summary
Abstract
1. Introduction
2. Lipid Utilization
2.1. Factors Regulating Substrate Availability
2.2. Factors Regulating Mitochondrial Biology
2.3. Transcription Factors
2.4. Extracellular Factors
3. Glucose Utilization
3.1. Factors Regulating Substrate Availability
3.2. Signaling Factors
3.3. Transcription Factors
3.4. Extracellular Factors
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene/Protein | Genetic Manipulation | Associated Function | Exercise Phenotype | Effects on Fuel Utilization | References |
---|---|---|---|---|---|
CD36 | Whole-body KO | Fatty acid transporter | Promote endurance exercise capacity | Promote fatty acid transport into muscle, allowing for metabolic switching | [14] |
ATGL | Whole-body KO | Triacylglycerol lipase | Promote endurance exercise capacity | Promote exercise-stimulated lipolysis | [19] |
HSL | Whole-body KO | Triacylglycerol lipase | Promote endurance exercise capacity | Promote exercise-stimulated lipolysis | [20] |
L-Carnitine | Overexpression (oral dose administered) | Cofactor for fatty acid transformation and transport | Enhance endurance exercise capacity | Promote fat utilization and mitochondrial biogenesis | [23] |
VEGF | Adipocyte-specific KO | Promotes angiogenesis | Promote exercise tolerance | Increase adipose capillarity, increasing bioavailability of free fatty acids | [25] |
OPA1 | Haplodeficiency | Regulate mitochondrial fusion | Not sufficient to affect exercise capacity by itself | Promote fatty acid oxidation | [30] |
NRF2 | Whole-body KO | Regulate genes in oxidative stress response | Promote endurance exercise capacity | Promote fatty acid oxidation | [33,34] |
KEAP1 | Muscle-specific KO | Negatively regulates NRF2 | Decrease endurance and resistance exercise capacity | Decreases fatty acid oxidation | [32] |
PGC-1a | Whole-body KO, Muscle-specific KO | Cotranscription factor that regulates fatty acid oxidation, mitochondrial biogenesis, and mitochondrial function | Promote exercise tolerance and slow-twitch muscle fiber content | Maintain glucose homeostasis, promote fatty acid oxidation | [35,37,38,39] |
Sestrins | Whole-body KO | Stress-induced protein, activates downstream pathways to regulate metabolism | Promote endurance exercise capacity | Maintain glucose homeostasis, promote fatty acid oxidation | [50] |
PPARα | Whole-body KO, muscle-specific overexpression | Transcription factor that regulates lipid and glucose homeostasis | Promote endurance exercise capacity | Favor lipid utilization over glucose, promotes fatty acid oxidation | [54,57,58] |
KLF15 | Whole-body KO | Transcription factor that regulates many metabolic processes | Promote endurance exercise capacity | Allows metabolic switching; promotes fatty acid oxidation in endurance exercise | [60] |
NR4A1 or NUR77 | Muscle-specific overexpression | Transcription factor that affects muscle fiber content | Increase muscle contractile function | Promotes fatty acid oxidation over glucose oxidation | [62] |
P50 (NF-κB) | Whole-body KO | Transcription factor that regulates inflammation and infection | Decrease endurance exercise capacity | Decreases fatty acid oxidation and promotes glucose oxidation | [64] |
Il-13 | Whole-body KO | Anti-inflammatory cytokine | Promote exercise capacity | Promote fatty acid oxidation and mitochondrial biogenesis | [67] |
ACSL1 | Muscle-specific KO | Directs fatty acids into mitochondria for fatty acid oxidation | Promote endurance exercise capacity | Promotes fatty acid oxidation over glucose use | [69] |
GYS | Muscle-specific KO | Key enzyme in synthesis of glycogen in skeletal muscle | Promote endurance exercise capacity | Maintains muscle glycogen for use as a fuel source | [72] |
AIFM2 | Muscle targeted KD and OE, muscle-specific haploinsufficiency (ACTA-Cre) | NADH oxidoreductase | Promote high-intensity exercise | Promote glucose utilization over lipid use | [74] |
S6K1 | Whole-body KO | Component of mTORC signaling pathway that controls cell growth | Decrease exercise capacity | Downregulate ketogenesis, and promote glucose utilization over fatty acid oxidation | [75] |
mTORC1 | Muscle-specific activation (via KO of negative regulators) | Regulator of protein translation and cellular metabolism | Muscle hypertrophy; no observed differences in exercise capacity | Increase glycolytic fibers in muscle, promoting glucose utilization | [76,77,78] |
AMPK | Whole-body KO | Whole-body stress sensing kinase that regulates energy metabolism | Promote exercise capacity | Promote mitochondrial content and glucose uptake | [80] |
PPARδ | Muscle-specific overexpression | Nuclear receptor that is a key regulator of fatty acid metabolism in muscle | Promote endurance exercise capacity | Stimulate fatty acid oxidation and suppress glucose utilization | [82] |
Myogenin | Whole-body KO | Regulates skeletal muscle development during embryonic and fetal stages | Decrease exercise capacity | Increase sensitivity to depletion of glycogen reserves; decreased efficiency of fatty acid and glucose use | [83] |
HIF-1α | Muscle-specific KO | Protein complex that responds to low oxygen conditions (hypoxia) | Decrease exercise capacity; prevent muscle damage from repeated exercise | Promotes glucose utilization over fatty acid oxidation | [85] |
Il-6 | Whole-body KO, muscle-specific KO, whole-body OE (injection), muscle-specific OE (injection) | Myokine believed to be largely anti-inflammatory | Increase exercise capacity | Increase fatty acid oxidation | [87,89,90,93] |
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Pi, A.; Villivalam, S.D.; Kang, S. The Molecular Mechanisms of Fuel Utilization during Exercise. Biology 2023, 12, 1450. https://doi.org/10.3390/biology12111450
Pi A, Villivalam SD, Kang S. The Molecular Mechanisms of Fuel Utilization during Exercise. Biology. 2023; 12(11):1450. https://doi.org/10.3390/biology12111450
Chicago/Turabian StylePi, Anna, Sneha Damal Villivalam, and Sona Kang. 2023. "The Molecular Mechanisms of Fuel Utilization during Exercise" Biology 12, no. 11: 1450. https://doi.org/10.3390/biology12111450
APA StylePi, A., Villivalam, S. D., & Kang, S. (2023). The Molecular Mechanisms of Fuel Utilization during Exercise. Biology, 12(11), 1450. https://doi.org/10.3390/biology12111450