Skeletal Muscle Health in Metabolic Diseases

Metabolic diseases such as obesity and diabetes cause disruption of systemic energy metabolism and are major public health problems, with at least 2 billion people affected worldwide. Skeletal muscle tissue makes a substantial contribution to promoting energy efficiency because it remodels cellular size, composition, and function in response to various nutritional changes. However, metabolic diseases such as impaired insulin sensitivity can dynamically affect the metabolism of skeletal muscle. A deeper understanding of myopathology in metabolic disorders may provide clues for therapeutic strategies to promote skeletal muscle health and improve the overall quality of life. This chapter presents how metabolic diseases via cellular mechanisms affect muscle cells and muscle tissue, especially glucose metabolism in skeletal muscle. 

Skeletal muscles and the liver share functions as metabolic organs, and there are known crosstalk in their pathophysiology. In today's world, where obesity is rampant, many people suffer from metabolic abnormalities associated with obesity, posing a global health issue. This chapter summarizes the latest findings on the crosstalk between metabolic dysfunction-associated steatotic liver disease (MASLD) and skeletal muscles, which starts and progresses in association with obesity and its associated systemic metabolic abnormalities.

People consume nutrients such as carbohydrates, fats, proteins, vitamins, and minerals in their diet. Among these, carbohydrates and fats are mainly used by the body as energy. Lipids are stored in the body mainly in the form of triglycerides, whereas carbohydrates are primarily stored in the liver and skeletal muscles in the form of glycogen. Compared to fat, glycogen can be stored in much smaller quantities in the body. Glycogen utilization has also been shown to increase during exercise. When glycogen is depleted, exercise performance is impaired. Glycogen is, therefore, a valuable source of energy, and much research has been conducted on how to store glycogen and how to enhance glycogen recovery after exercise. In addition, managing glucose and glycogen through proper nutrition and exercise training is very important not only for improving athletic performance but also for maintaining and improving health. Therefore, this chapter focuses on the impact of nutrition and exercise on carbohydrate metabolism.

Modern lifestyles, such as a Western diet, excessive food consumption, and physical inactivity, are closely associated with brain health and noncommunicable diseases, including type 2 diabetes. Epidemiological evidence suggests that an unhealthy lifestyle leads to impaired brain health, manifesting in conditions such as depression and anxiety. Conversely, mental illness can contribute to the development of type 2 diabetes. Thus, it has been suggested that there is a bidirectional relationship between brain health and metabolic diseases, but the detailed mechanisms remain unclear.

Exercise is considered the primary choice for the treatment of obesity or type 2 diabetes. This is attributed to the fact that increased physical activity contributes to a reduction in body weight and the accumulation of excess adipose tissue. Furthermore, it has long been recognized that exercise enhances brain health. Recent studies have revealed that, in addition to these indirect effects, exercise exerts its beneficial effects by releasing bioactive substances. This chapter presents how metabolic diseases affect brain health and how exercise mitigates these detrimental effects, focusing particularly on the molecular mechanisms in the brain. 

Obesity and diabetes are associated with changes in skeletal muscle quantity and quality, such as increased ectopic fat, muscle atrophy, and decreased muscle strength. Skeletal muscle tissue is often affected by metabolic insult because it remodels cellular size, composition, and function in response to a variety of nutritional changes. Declining muscle quantity and quality are directly linked to falls and bedriddenness; understanding the intracellular mechanisms may provide clues for therapeutic strategies. How metabolic diseases via cellular mechanisms affect muscle quality and muscle quantity are presented in this chapter.

Obesity and diabetes impair skeletal muscle metabolism, muscle atrophy, and contractile function, but the intracellular mechanisms have not been clarified fully. Increasing evidence suggests that oxidative stress is associated with obesity and diabetes. Depending on the pathological condition, stress may be affected to a greater extent. Muscle oxidative stress has been implicated in lipid species composition in type 2 diabetes. This chapter discusses the impact of metabolic disease on the regulation of lipid species and oxidative stress.