Absorptive vs. Post-Absorptive Metabolic States

• These notes will cover the metabolic differences between the absorptive (feeding) state and the post-absorptive (fasting) state.

The Absorptive State

• The absorptive state lasts about 2-4 hours after a normal meal.
• There are transient increases in plasma glucose, amino acids, and triacylglycerols (TAG).
• The islet tissue of the pancreas responds to elevated glucose levels by an increased secretion of insulin, and a decreased release of glucagon.
• An elevated insulin-to-glucagon ratio and the availability of circulating substrates makes the absorptive state an anabolic period.
• There is increased synthesis of TAG and glycogen to replenish fuel stores, and an enhanced synthesis of protein.
• During this state, most tissues use glucose as fuel.
• Body's metabolic response mainly alters metabolism in the liver, adipose tissue, skeletal muscle, and brain.

Fasting

• Fasting begins if no food is摄入after the absorptive period.
• Fasting may result from an inability to obtain food, rapid weight loss efforts, or clinical situations where individuals cannot eat.
• Without food, plasma levels of glucose, amino acids, and TAG decline, triggering decreased insulin secretion and an increase in glucagon andepinephrine release.
• The body adjusts to maintain essential fuel supplies during the decreased insulin/counter-regulatoryhormone ratio and the decreased availability of circulating substrates
• The period is characterized by the degradation of glycogen, fats and proteins Two Metabolic Priorities in Fasting:
• Maintaining adequate plasma glucose levels to meet the energy needs of the brain and red blood cells.
• Mobilizing fatty from adipose tissue and synthesizing ketone bodies in the liver.

Fuel Stores (70 kg man at the beginning of a fast)

• Fat: 15 kg = 135,000 kcal
• Protein: 6 kg = 24,000 kcal
• Glycogen: 0.2 kg = 800 kcal

Carbohydrate Metabolism

In the well-fed period, liver glucose uptake rises (independent of insulin), phosphate and glycogen synthesis increase, and glycolysis spikes post-meals, while gluconeogenesis and glycogenolysis decrease. Fasting enhances glycogen degradation and glucose synthesis.

Fat Metabolism

Well-fed phases see increased fatty acid and triacylglycerol synthesis, while fasting boosts fatty acid oxidation and ketone body formation for fuel.

Protein Metabolism

Protein synthesis rises to replace degraded proteins, and amino acid degradation decreases.

Carbohydrate Metabolism in Adipose Tissue

During the Well-Fed Period:

• There is increased glucose transport (GLUT4, Insulin dependent), and glycolysis (glycerol 3-phosphate for TAG synthesis).

During Fasting:

• Glucose transport decreases (because of declined insulin levels.)

Fat Metabolism in Adipose Tissue

During the Well-Fed Period:

• Most fatty acids added to TAG stores of adipocytes after eating lipids are provided by the degradation of dietary TAG from the intestine and endogenous TAG from the liver (VLDL).

During Fasting:

• There is increased fat degradation, increased fatty acid release, and decreased fatty acid uptake.

Carbohydrate Metabolism in Resting Skeletal Muscle

During the Well-Fed Period:

• There is an increase in glucose transport into muscle cells by GLUT-4, and an increased glycogen synthesis.

During Fasting:

• Resting skeletal muscle switches its primary fuel source from glucose to fatty acids.
• Glucose transport into skeletal muscle cells occurs via insulin-sensitive GLUT-4, and subsequent glucose metabolism are depressed due to low circulating insulin levels.
• Hepatic gluconeogenesis is unavailable to both muscle and adipose tissue.

Protein Metabolism in Resting Skeletal Muscle During the Well-Fed Period:

• There is increased protein synthesis and uptake of amino acids.

During Fasting:

• During the first days of fasting, there is a breakdown of muscle protein, providing amino acids used by the liver for gluconeogenesis.
• In second week of fasting rate of muscle protein breakdown slows, paralleling a decline in the need for brain glucose.

Fat Metabolism in Resting Skeletal Muscle

During the Well-Fed Period:

• Fatty acids are used as a fuel for resting muscle during the period, however glucose the primary fuel.

During Fasting:

• Muscle uses fatty acids and ketone bodies as fuels and spares glucose and protein.
• This usage continues for the initial 2 weeks.
• After approximately 3 weeks, muscle spares the glucose and protein by almost exclusively fatty acids.

Brain Metabolism

• The brain exclusively uses glucose taken-up via GLUT- 1 of the BBB, completely oxidizing it into CO2 and H2O.
• The glycogen reserve in the brain is small, meaning it is completely dependent on the availability of blood glucose.
• Cerebral malfunction begins if blood glucose levels fall below 40 mg/100 ml.
• The brain does not use fatty acids for energy because these do not readily cross the BBB.
• During early fasting, brain continues to use only glucose as fuel, sustained by hepatic gluconeogenesis.
• With prolonged fasting, plasma ketone bodies reach significantly elevated levels, becoming the brain's primary fuel source.
• This reduces the need for protein catabolism involved in gluconeogenesis. As the duration extends from overnight to weeks, blood glucose levels initially drop and then are maintained at 65-70 mg/dl.

Kidney Metabolism During Long Term Fasting

• Kidneys contribute significantly to gluconeogenesis.
• There is increased ammonium production.

Role of Insulin

• Insulin decreases blood glucose, amino acids, fatty acids, and ketoacid, and increases potassium levels.
• Insulin increases cell glucose transport, glycogen synthesis, lipogenesis, protein synthesis ,etc.
• Insulin decreases glycogenolysis, gluconeogenesis, lipolysis et.

Role of Glucagon

• Glucagon increases blood glucose, fatty acids, and ketoacid levels.
• Galucagon Increases glycogenolysis, gluconeogenesis, and lipolysis.
• Cortisol at basal levels aids both gluconeogenesis and lipolysis during postabsorptive states.
• High cortisol plasma levels result in increases in
  • Protein catabolism.
  • Gluconeogenesis.
  • Triglyceride breakdown.
  • Decreased uptake of glucose by both muscle cells and adipose tissue cells.
• Endocrine counter-regulatory controls are regulated by glucagon, epinephrine, cortisol, and growth hormone.
• The process of glycogenolysis is stimulated by glucagon and epinephrine.
• Meanwhile, gluconeogenesis and lipolysis is stimulated by all, but in differing amounts

Exploration of the metabolic differences between the absorptive (feeding) and post-absorptive (fasting) states. Focus on the roles of insulin and glucagon in regulating glucose, amino acid, and triacylglycerol metabolism during these periods.