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Fed State Metabolism

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Fed State: Introduction - Fuel Flood Fiesta

  • Aka: Absorptive / Post-prandial state.
  • Timing: Begins after nutrient ingestion; lasts 2-4 hours.
  • Hallmark: "Fuel Flood" - influx of glucose, amino acids, fats (chylomicrons).
  • Primary Driver: ↑ Insulin secretion (pancreatic β-cells).
    • Responds to ↑ blood glucose & amino acids.
  • Hormonal Milieu:
    • ↑ Insulin : Glucagon ratio.
    • ↓ Glucagon, ↓ Epinephrine, ↓ Cortisol.
  • Overall Goal: Anabolism - utilize & store incoming nutrients.
    • Energy needs met by absorbed glucose.
    • Excess nutrients stored: Glycogen, Triacylglycerols (TAGs), Proteins.

⭐ Insulin is the major anabolic hormone of the fed state, promoting synthesis and storage of nutrients. Fed State Liver Metabolism Pathways

Fed State: Carbohydrates - Sugar Stash & Burn

  • Stimulus: ↑ Post-meal blood glucose.
  • Key Hormone: Insulin.
  • Effects: Glucose uptake, glycogenesis, glycolysis, lipogenesis.
  • Liver (GLUT2; pathways insulin-stimulated):
    • ↑ Glycogenesis (storage).
    • ↑ Glycolysis (ATP, Acetyl-CoA for FA synthesis).
    • ↑ PPP (NADPH for FA synthesis).
    • ↑ FA synthesis, VLDL export.
  • Muscle (GLUT4, insulin-dependent):
    • ↑ Glucose uptake.
    • ↑ Glycogenesis (storage).
    • ↑ Glycolysis (ATP).
  • Adipose (GLUT4, insulin-dependent):
    • ↑ Glucose uptake.
    • ↑ Glycolysis (Glycerol-3P for TGs).
    • ↑ TG storage.
  • Brain (GLUT1/3), RBCs (GLUT1): Insulin-independent glucose use. RBCs: anaerobic glycolysis.

⭐ GLUT4, found in muscle and adipose tissue, is the insulin-responsive glucose transporter crucial for postprandial glucose uptake.

📌 GLUTs: 1(RBC/Brain), 2(Liver/Pancreas), 4(Muscle/Adipose, Insulin ↑).

Glucose Metabolism in the Fed State

Fed State: Lipids & Proteins - Fat Packing & Building

  • Lipid Metabolism (Storage Dominates):
    • Dietary Fats (Chylomicrons, CM):
      • CMs transport dietary TGs.
      • Insulin & Apo C-II activate Lipoprotein Lipase (LPL).
      • LPL: TGs (CM/VLDL) → FAs + Glycerol. FAs enter adipose/muscle.
    • Liver-derived Fats (VLDL):
      • Excess calories → De Novo Lipogenesis (liver) → TGs → VLDL.
    • Adipose Tissue (Insulin's Role):
      • ↑ GLUT4 uptake, ↑ Glycolysis (Glycerol-3-P for TG synthesis).
      • ↑ LPL activity (FA uptake), ↓ Hormone-Sensitive Lipase (HSL) activity (prevents lipolysis). Fed state lipid metabolism: chylomicron and VLDL processing
  • Protein Metabolism (Synthesis Focus):
    • Amino Acids (AAs):
      • Liver: Synthesizes plasma proteins (e.g., albumin), non-essential AAs. Excess AAs → energy/fat precursors; N → urea.
      • Peripheral Tissues: Insulin ↑ AA uptake & protein synthesis (muscle).

⭐ Insulin promotes TG storage by activating LPL (FA uptake from CM/VLDL) & inhibiting HSL (prevents fat breakdown) in adipose tissue during fed state.

Fed State: Organ Integration - Metabolic Symphony

High insulin:glucagon ratio orchestrates metabolic harmony post-meal.

OrganFed State Role (Insulin ↑)
LiverGlucose → Glycogen; Excess Glucose/AA → FAs → TGs (VLDL); Protein synthesis.
MuscleGlucose uptake (GLUT4) → Glycogen, ATP; Protein synthesis.
AdiposeGlucose uptake (GLUT4) → Glycerol-3P; FAs (Chylomicrons, VLDL via LPL) → TGs (storage).
BrainGlucose uptake (GLUT1/3); Primary fuel.
RBCsGlucose uptake (GLUT1); Anaerobic glycolysis ($2$ ATP/glucose).

High‑Yield Points - ⚡ Biggest Takeaways

  • Insulin is the dominant hormone; glucagon is suppressed.
  • Glucose is the primary fuel for most tissues.
  • Liver: ↑ glycogenesis, ↑ lipogenesis from excess glucose, ↑ protein synthesis.
  • Adipose tissue: ↑ glucose uptake (GLUT4), ↑ triglyceride synthesis & storage; LPL active.
  • Muscle: ↑ glucose uptake (GLUT4), ↑ glycogen synthesis, ↑ protein synthesis.
  • Brain utilizes glucose (insulin-independent uptake).
  • RBCs rely on anaerobic glycolysis of glucose.

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