Systemic Energy Substrate Utilization describes the body-wide process of selecting, mobilizing, and oxidizing macronutrients—primarily carbohydrates, fats, and proteins—to meet the energetic demands of all tissues. This metabolic flexibility is under tight hormonal control, dynamically shifting between substrates based on nutritional status, activity level, and time of day. Optimal utilization is a marker of excellent metabolic health and hormonal balance, ensuring efficient fuel delivery to the brain and muscle. Dysregulation in this process is characteristic of metabolic syndrome.
Origin
This term is a core concept in human physiology and metabolism, integrating the roles of multiple organs in energy balance. Substrate Utilization refers to the consumption of fuel sources, and the “Systemic” component emphasizes the coordination across the entire organism. Its clinical importance has grown with the recognition of metabolic inflexibility as a root cause of chronic disease.
Mechanism
The mechanism is primarily regulated by the opposing actions of insulin and glucagon, alongside catecholamines and cortisol. During fasting, glucagon promotes gluconeogenesis and lipolysis, shifting utilization toward fat. Following a meal, insulin drives glucose uptake and storage, shifting utilization toward carbohydrates. Exercise and hormonal balance modulate the activity of key enzymes in muscle and liver that govern the entry of these substrates into the tricarboxylic acid cycle for ATP production.
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