Lipid Mobilization and Lipid Transport
High-Yield Summary
- Post-absorptive state: falling insulin + rising epinephrine/glucagon/cortisol activate hormone-sensitive lipase (HSL) in adipose tissue, splitting triglycerides into glycerol + free fatty acids.
- Glycerol → liver → gluconeogenesis (adipose lacks the enzymes to use glycerol itself). Fatty acids → bind albumin → tissues for beta-oxidation; excess liver acetyl-CoA (when oxaloacetate is diverted to gluconeogenesis) → ketogenesis.
- Lipoproteins solve blood transport of hydrophobic lipids; classified by density — more protein = higher density. Order: chylomicron → VLDL → IDL → LDL → HDL (increasing protein/density, generally).
- Chylomicrons (dietary) and VLDL (liver-made) both lose triglycerides via lipoprotein lipase; VLDL → IDL → LDL. LDL delivers cholesterol to cells; HDL performs reverse cholesterol transport back to the liver.
- Apolipoproteins direct each particle: ApoB-48 (chylomicron formation), ApoB-100 (LDL receptor recognition), ApoC-II (activates lipoprotein lipase), ApoE (liver uptake of remnants), ApoA-I (activates LCAT).
Key Terms
- Hormone-sensitive lipase (HSL)
- Enzyme in adipocytes that breaks triglycerides into glycerol and free fatty acids; activated by low insulin/high catecholamines.
- Lipoprotein lipase
- Capillary-surface enzyme stripping triglycerides from chylomicrons/VLDL for tissue uptake.
- Reverse cholesterol transport
- HDL's role: collecting excess cholesterol from tissues and returning it to the liver.
Lipolysis and Fuel Routing
- 1Insulin falls, epinephrine/glucagon/cortisol rise (post-absorptive state)
- 2Hormone-sensitive lipase activates in adipose tissue
- 3Triglycerides split into glycerol and free fatty acids
- 4Glycerol → liver → gluconeogenesis
- 5Fatty acids (bound to albumin) → tissues → beta-oxidation; liver excess acetyl-CoA → ketogenesis
The Five Major Lipoproteins
| Lipoprotein | Origin / Main Cargo / Function |
|---|---|
| Chylomicron | Intestinal cells / Dietary triglycerides / Transport dietary lipids |
| VLDL | Liver / Liver-made triglycerides / Transport TGs to tissues |
| IDL | VLDL after TG loss / TGs + cholesterol / Intermediate — liver uptake or becomes LDL |
| LDL | IDL after further TG loss / Cholesterol / Deliver cholesterol to cells |
| HDL | Liver and intestines / Cholesterol (protein-rich) / Reverse cholesterol transport |
Apolipoproteins
| Apolipoprotein | Role |
|---|---|
| ApoA-I | Activates LCAT (cholesterol esterification into HDL) |
| ApoB-48 | Required for chylomicron formation/secretion |
| ApoB-100 | LDL receptor recognition signal |
| ApoC-II | Activates lipoprotein lipase |
| ApoE | Liver recognition of chylomicron/VLDL remnants |
Common MCAT Trap
- Adipose tissue can't use glycerol itself — it lacks the enzyme to phosphorylate it — so glycerol always goes to the liver.
- Higher lipoprotein density = MORE protein, not more lipid — LDL ('bad') is less dense than HDL ('good'), an easy inversion trap.
- The liver making ketone bodies vs. peripheral tissues using them is a division of labor — don't assume the liver benefits from its own ketogenesis output.
Quick Recall
What activates hormone-sensitive lipase?
Which apolipoprotein activates lipoprotein lipase?
What is HDL's main job?