ii. Metabolism

Master answer

Body energy substrate reserves and utilisation

Fuel homeostasis principally regulates the needs of brain and muscle (major consumers of fuel).
brain – glucose exclusively (120g/d) until prolonged starvation (~2 days) then switches to ketones (fuel sparing)

Body energy substrate reserves:

• Glycogen stores → source of glucose (sufficient for brief period of fasting <24hrs)
  • Liver (100 g; ½ day supply)
  • Muscle (400 g)
  • Brain (minimal; 4 mins supply)
• Fat stores (as TAG) → source of FFA and glycerol
  • liver and adipose tissue
• Protein stores → source of a.a.
  • muscle protein, plasma proteins, CT, enzymes

Body energy substrate utilisation:

• Brain/nervous tissue – 1°ly uses glucose for energy, but uses KBs with fasting
• Cardiac muscle – Use FFA, lactate and KB for energy
• RBC – 1°ly uses glucose for energy
• Skeletal muscle
  • Uses FFA and ketone bodies for energy
  • Glucose can be used for energy (esp with hyperglycaemia or anaerobi conditions (Eg. exercise)) or glycogen storage
• Adipose tissue – Uptake of glucose, glycerol and FFA → forms TAG for storage (lipogenesis); also breaks TAG into FFA/glycerol (lipolysis)
• Liver → integral role in starvation
  • Control BSL by controlling glycogen stores and gluconeogenesis
  • Takes up all metabolic fuel substrates → can interconvert them (Eg. gluconeogenesis, ketogenesis)
• Vital source of circulating metabolic fuel substrates

Glucose Homeostasis

Metabolic responses to starvation

<24 hrs (early fasting)

• Initially Phase I and dietary glucose metabolized
• Phase II starts when dietary glucose exhausted
• ↓ Insulin
• Hepatic glycogenolysis maintains blood glucose
• Transient increase metabolic rate

24-72 hrs (short-term)

• Phase II starts when Glycogen stores exhaust around 20hrs
• depending on: feeding status, hepatic glycogen stores, physical activity
• ↓ Insulin ↑ Glucagon and ↑ catecholamine
• Brain and RBCs: Glucose from Hepatic Gluconeogenesis (from lactate, pyruvate, glycerol and alanine)
• Other (skeletal and cardiac muscle, kidney, liver): FFAs + glycerol (from Lipolysis / Hydrolysis of TGs)
• Metabolic rate begins to decrease after 48hrs

>72 hrs (Prolonged)

• ↓↓↓ Insulin ↑ Glucagon and ↑catecholamine
• Phase IV starts after several days of fasting
  • Gluconeogenesis starts to decrease
  • Ketone body accumulation increases
  • Brain uses both glucose and ketone body for energy
• Further decline in metabolic rate 15-20%
• Phase V starts after prolonged fasting
  • Less dependence on gluconeogenesis
  • All tissues use Fatty acid and Ketone body oxidation for energy
• High ketone body conc, and glucose levels inhibit proteolysis (conservation of muscle) (protein sparing effect)
• After fat and ketone body exhausted → starvation → proteolysis of muscle
• Reduced energy expenditure
  • reduced diet induced thermogenesis
  • reduced weight and energy cost of movement
  • decline in voluntary physical activity