Metabolic Integration During Fasting

Metabolic Integration During Fasting

• Fasting triggers a cascade of metabolic adjustments across various organs to maintain energy balance.
• Initial fasting relies on glycogenolysis (liver glycogen breakdown), while prolonged fasting necessitates gluconeogenesis (glucose production from non-carbohydrate sources like amino acids and glycerol).
• Fatty acid oxidation becomes crucial, providing energy, and ketone bodies become an important fuel source, especially for the brain.
• The liver plays a central role in glucose homeostasis during fasting, driving glycogenolysis and gluconeogenesis to keep blood glucose levels stable.
• During prolonged fasting, the body transitions towards using fatty acids and ketone bodies for fuel to preserve glucose stores for the brain and other vital organs.
• Muscle protein breakdown supports gluconeogenesis, providing amino acids for glucose synthesis.
• Reduced metabolic rate, a consequence of decreased thyroid hormone (T3) levels, helps conserve energy reserves in prolonged fasting.

Role of Hormones During Fasting

• Insulin: An anabolic hormone stimulating glucose uptake, glycogen synthesis, and lipid storage. Low insulin levels during fasting are crucial for mobilizing energy stores.
• Glucagon: A catabolic hormone promoting glycogenolysis and gluconeogenesis to maintain blood glucose levels.
• Adrenaline (epinephrine): A rapid-response hormone increasing blood glucose via glycogenolysis and lipolysis, especially during stress or low blood glucose.
• Cortisol: A long-term stress hormone affecting metabolism by increasing glycogenolysis, lipolysis, inhibiting peripheral glucose utilization, and stimulating gluconeogenesis and protein breakdown, which is important in adapting to prolonged fasting. The long term effects of excess cortisol can have detrimental impacts including hyperglycemia, insulin resistance and fat redistribution

Organ-Specific Adaptations

• Liver: Central to glucose homeostasis, it performs glycogenolysis and gluconeogenesis. It produces ketone bodies from fatty acids for energy during fasting.
• Adipose tissue: Releases fatty acids into the bloodstream for energy utilization by other tissues during fasting.
• Skeletal Muscle: Initially uses stored glycogen and then shifts to fatty acids and ketone bodies, preserving muscle protein for vital functions during prolonged fasting.
• Brain: Primarily relies on glucose, but adapts to use ketone bodies during prolonged fasting.
• Kidney: Supports gluconeogenesis during fasting, helping to maintain blood glucose levels.

Metabolic States

• Post-prandial (fed): High insulin levels promote glucose uptake and energy storage (glycogen and triglycerides).
• Fasting: Glycogen breakdown and gluconeogenesis are prioritized to maintain blood glucose levels.
• Starvation: A prolonged fasting state, where the body adapts to utilizing fatty acids and ketone bodies extensively as primary fuel sources.

Energy Sources During Fasting

• Carbohydrates: Limited storage, primarily glycogen. Liver glycogen is first used, followed by gluconeogenesis.
• Lipids: Adipose tissue triglycerides provide a major source of energy during extended fasting.
• Proteins: Breakdown of muscle proteins contributes to gluconeogenesis during prolonged fasting.

Brain Fuel Adaptation

• Glucose: Primary energy source in the fed state and for a limited time during fasting.
• Ketone bodies: Crucial alternative fuel source for the brain during prolonged fasting to prevent glucose depletion.

Physical Exercise (Anaerobic and Aerobic):

• Anaerobic Exercise: Muscles initially utilize phosphocreatine and ATP stores to regenerate ATP; glycogen breakdown to lactate later.
• Aerobic Exercise: Muscle cells rely mostly on aerobic metabolism, utilizing fatty acids (or ketone bodies during extended fasting/glycogen depletion) for energy.