U01.01.129 Fasted vs fed state

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Learning Objectives

  • Differentiate the roles of Hormone-Sensitive Lipase (HSL) and Lipoprotein Lipase (LPL).
  • Explain how Insulin, Glucagon, and Epinephrine reciprocally regulate lipid storage and mobilization.
  • Identify the importance of Apo CII in activating fatty acid uptake.
  • Understand the requirement of Glucose/DHAP for triacylglycerol (TG) synthesis in adipocytes.

1. The Fasted State: Lipid Mobilization

In the fasted state, the body needs to mobilize stored energy. This occurs via lipolysis in the adipocyte.

  • Hormonal Trigger: Glucagon and Epinephrine bind to G-protein-coupled receptors.
  • Signaling: This increases cAMP, which activates Protein Kinase A (PKA).
  • Key Enzyme: PKA phosphorylates and activates Hormone-Sensitive Lipase (HSL).
  • Outcome: HSL breaks down Triacylglycerols (TG) into Glycerol and Free Fatty Acids (FFA), which are released into the blood.
    • Glycerol: Travels to the liver for gluconeogenesis.
    • FFA: Travels to tissues (bound to albumin) for \beta-oxidation.

2. The Fed State: Lipid Storage

In the fed state, the body stores excess energy as fat. Insulin promotes the uptake of triglycerides from circulating lipoproteins (Chylomicrons and VLDLs).

  • Hormonal Trigger: Insulin.
  • Key Enzyme: Lipoprotein Lipase (LPL). Insulin stimulates LPL synthesis and its movement to the capillary endothelium.
  • Activation: LPL is activated by Apo CII on the surface of lipoproteins.
  • TG Synthesis (Esterification):
    • Adipocytes lack glycerol kinase, so they cannot use free glycerol.
    • Instead, they take up Glucose (via GLUT4), convert it to DHAP, and then to Glycerol 3-Phosphate.
    • This Glycerol 3-P is combined with incoming FFAs to form stored **TG**.

Activity: Lipase Logic Challenge

3. Comparison Table: HSL vs. LPL

Feature Hormone-Sensitive Lipase (HSL) Lipoprotein Lipase (LPL)
Primary State Fasted / Starvation Fed / Postprandial
Location Inside the adipocyte cytosol Vascular endothelial surface
Function Breaks down stored fat to release energy Cleaves circulating TGs for storage
Effect of Insulin Inhibits (via dephosphorylation) Stimulates (Synthesis/Expression)
Clinical Notes & Corrections:

  • Diabetic Ketoacidosis (DKA): In Type 1 Diabetes, the total lack of insulin leads to unopposed HSL activity. This floods the liver with FFAs, which are then converted into massive amounts of ketones.
  • Essential Intermediate: Remember that Glucose is required for fat storage in the fed state because it provides the glycerol backbone (via DHAP). Without glucose entry, adipocytes cannot store fat effectively.

 

Memory Hook: HSL = Hunger Signals Lipolysis. LPL = Lots of Pandemic Lipids (storing them away).

Activity