Learning Objective
Understand the regulation of Hormone-Sensitive Lipase (HSL) by hormonal signaling pathways and master the utilization of post-lipolysis products (free fatty acids and glycerol) by various tissues during starvation.
High-Yield Lipolysis Pathway & Tissue Utilization
| Hormone / Tissue | Mechanism / Activators | Inhibitors / Substrate Utilization |
|---|---|---|
| Hormone-Sensitive Lipase (HSL) | Activated by: Stress hormones (Catecholamines, Glucagon, ACTH) Pathway: Gs → cAMP ↑ → PKA → Phosphorylation of HSL |
Inhibited by: Insulin Action: Cleaves stored triglycerides → FFAs + Glycerol |
| Liver | Glycerol → Carbon source for Gluconeogenesis | FFAs → oxidized to Acetyl-CoA → Ketone bodies (Acetoacetate, β-hydroxybutyrate) or TCA cycle |
| Brain | Can use Ketone bodies & Glucose | Cannot use FFAs (FFAs do not cross the Blood-Brain Barrier) |
| Erythrocytes (RBCs) | Can use Glucose ONLY | Cannot use FFAs or Ketones (RBCs lack mitochondria) |
Core High-Yield Concepts for NEET PG
- HSL Molecular Regulation: HSL is active when phosphorylated. Stress hormones trigger the $G_s$ → Adenylate Cyclase → cAMP → Protein Kinase A (PKA) cascade to phosphorylate the enzyme.
- Insulin Action: Insulin counteracts this mechanism by inducing HSL dephosphorylation, effectively halting lipolysis in the well-fed state.
- Energy Dynamics in Starvation: The energy derived from hepatic β-oxidation of FFAs provides the ATP required to drive energy-expensive gluconeogenesis.
Critical Exam Discriminators
- RBC Fuel Source: Because erythrocytes completely lack mitochondria, they are strictly dependent on anaerobic glycolysis (glucose). They can never oxidize fatty acids or utilize ketone bodies.
- The Blood-Brain Barrier (BBB) Trap: Free fatty acids cannot cross the BBB due to their structural limitations and binding to albumin. The brain seamlessly transitions to utilizing water-soluble ketone bodies during prolonged starvation, reducing its overall reliance on glucose.