The Endurance Athletes' Paradox: Relationship between Muscle Tissue Fat Accumulation and Insulin Sensitivity in Endurance Athletes and Obese Individuals

Introduction
The relationship between intramyocellular lipid (IMCL) content and insulin sensitivity presents a fascinating paradox. In obese and diabetic individuals, elevated IMCL levels are associated with insulin resistance, impaired glucose uptake, and metabolic dysfunction. Conversely, endurance athletes, despite having higher IMCL levels, exhibit enhanced insulin sensitivity and superior metabolic health. This paradox underscores the complex interplay between IMCL, muscle fiber composition, lipid droplet proteins, and cytokines in determining metabolic outcomes.
This review explores the mechanisms underlying the endurance athlete's paradox, focusing on the roles of muscle fiber types, lipid droplet-associated proteins, and myokines such as interleukin-6 (IL-6) and interleukin-15 (IL-15). By elucidating these mechanisms, we aim to provide insights into potential therapeutic strategies for improving insulin sensitivity in obese populations.
This narrative review synthesizes findings from peer-reviewed studies on IMCL, lipid droplet proteins, and myokines in the context of insulin sensitivity and muscle metabolism. Key databases, including PubMed, Web of Science, and Google Scholar, were searched for relevant literature up to September 2024. Studies were selected based on their relevance to IMCL, muscle fiber types, lipid droplet proteins, and myokines in endurance athletes and obese individuals.
 
The role of exercise training on muscle fat content
As obesity and fat reserves increase, insulin sensitivity tends to decrease. Diabetic and obese individuals have higher levels of Intramyocellular Lipid (IMCL) compared to lean individuals. The increased intra-muscular fat content in obese individuals can impair glucose uptake by muscles, which may reduce insulin sensitivity. Interestingly, despite the higher fat content in their muscles, the oxidation of fatty acids appears to be impaired in obese individuals. Studies suggest that the skeletal muscle of obese individuals lacks the metabolic adaptation necessary to respond effectively to lipid exposure. This may result from an inability to enhance mitochondrial respiration in the presence of lipid substrates, as well as a failure to induce mitochondrial proliferation. However, it seems that endurance athletes are an exception. Their muscles contain more IMCL than those of lean individuals. It is a debated topic as to why the increase in triacylglycerol (TAG) in endurance athletes is linked with improved insulin sensitivity, while in obese and diabetic individuals, it is associated with increased insulin resistance. This paradox highlights the complex relationship between IMCL, metabolism, and insulin resistance in different populations.
Since the amount of type I fibers in insulin-sensitive obese people is higher than in insulin-resistant obese people, it is believed that type I fibers have a higher buffering ability for increased levels of IMCL, so they can prevent increased levels of ceramide and lipotoxicity. It has been shown that the content of IMCL in the subsarcolemma (SS) of type II fibers of diabetic subjects is four times higher than that of exercised subjects. It is proposed that in type II muscle fibers IMCL content, size and number of SS area LDs are negatively related to insulin sensitivity.
 
The role of lipid droplet proteins in endurance athletes' paradox
Lipid droplets in muscle tissue are surrounded by proteins essential for their metabolism and signaling. These proteins help mediate interactions with other cellular components and regulate the droplets' positioning. Studies suggest lipid droplets can recruit proteins for fat hydrolysis or storage. Decreased perilipin 3 (PLIN3) levels in obese individuals may lead to higher intramyocellular lipid (IMCL) levels, while PLIN2 is typically lower in lean than in obese individuals. Research indicates that PLIN2-deficient mice are resistant to diet-induced obesity. This resistance can be attributed to a reduction in food consumption and an increase in physical activity levels. Additionally, evidence suggests that genetic inhibition of PLIN2 is associated with a decrease in the size of lipid droplets.
In general, the content of PLIN2 is observed to increase in individuals with higher levels of adiposity. Endurance athletes, characterized by an elevated fat oxidation rate and increased levels of PLIN5, are believed to enhance PLIN5 expression in muscle cells in response to exercise stimuli. Conversely, it is noted that muscle cells in lean individuals and those with diabetes are inclined to elevate PLIN3 levels. It is posited that the skeletal muscles of athletes utilize PLIN5 to facilitate the storage of fat reserves, subsequently optimizing the oxidation of fat droplets for energy. This hypothesis may be elucidated through the interaction between PLIN5 and adipose triglyceride lipase (ATGL). PLIN5 demonstrates an ability to associate with ATGL, and its capacity to sequester ATGL at the membrane highlights the critical role that PLIN5 plays in lipase activity.
 
The role of IL-6 and IL-15 in endurance athletes' paradox
Changes in body composition correlate with alterations in cytokine secretion, particularly interleukin-6 (IL-6), a pro-inflammatory cytokine crucial for immune response. Research shows that muscle-derived IL-6 is linked to lipid metabolism rather than inflammation, and while obesity is associated with higher IL-6 levels, IL-6 may also facilitate intramuscular fat storage. IL-15, another important myokine, helps regulate fat metabolism in skeletal muscles and is linked to reduced adipocyte fat accumulation. Circulating IL-15 levels negatively correlate with body fat mass. While training status can influence the IL-6 response to exercise, it's less significant than factors like training intensity and duration. Notably, exercise increases IL-15 levels, but training does not affect its baseline levels.
 
 
Conclusion
The relationship between intramuscular fat content and insulin sensitivity presents a complex paradox, particularly when comparing obese individuals to endurance athletes. Research indicates that while both groups exhibit higher levels of IMCL, the implications for insulin sensitivity differ significantly. In obese individuals, increased IMCL is associated with impaired glucose uptake and reduced insulin sensitivity, potentially due to a lack of metabolic adaptation and mitochondrial dysfunction in response to lipid exposure. Conversely, endurance athletes, despite having greater IMCL, demonstrate improved insulin sensitivity, suggesting that the context of fat accumulation such as the size and location of lipid droplets, the presence of specific proteins like PLIN and the roles of myokines such as IL-6 and IL-15 plays a critical role in metabolic outcomes. The differential effects of IMCL on metabolism highlight the necessity for further research to elucidate the underlying mechanisms that allow endurance athletes to utilize intramuscular fat effectively while avoiding the metabolic dysfunction observed in obesity. Understanding these distinctions may provide insights into potential therapeutic strategies for improving insulin sensitivity in obese populations.
 Article Message
It appears that the mere increase in intramuscular fat content does not significantly contribute to heightened insulin resistance. The literature suggests that factors such as the specific locations of fat storage, the size of fat droplets, the types of bioactive lipids present, metabolic adaptation, associated coat proteins, and cytokines may contribute to the observed paradox of muscle fat accumulation in endurance athletes.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Authors' Contributions
All authors participated in designing, implementing, and writing all parts of the present study.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Acknowledgments
The researchers wish to extend their sincere appreciation to the esteemed officials of the Faculty of Physical Education and Sports Sciences at Guilan University.