Lipid digestion is a complex process that starts in the mouth and ends in the small intestine. Enzymes like lingual lipase, gastric lipase, and pancreatic lipase break down fats into smaller molecules. Bile salts help by making fat droplets easier to digest.

Once broken down, lipids are absorbed by cells in the small intestine. They're then packaged into chylomicrons and sent to the bloodstream. From there, different types of lipoproteins transport fats and cholesterol throughout the body for various uses.

Lipid Digestion in the GI Tract

Enzymatic Breakdown of Lipids

• Lingual lipase initiates lipid digestion in the mouth
  • Breaks down short-chain triglycerides
  • Limited activity due to short oral transit time
• Gastric lipase continues digestion in the stomach
  • Hydrolyzes medium-chain triglycerides
  • Accounts for 10-30% of total triglyceride digestion
• Pancreatic lipase performs primary triglyceride hydrolysis in the small intestine
  • Cleaves long-chain triglycerides into monoglycerides and free fatty acids
  • Responsible for 70-90% of total fat digestion

Role of Bile and Other Enzymes

• Bile salts enhance lipid digestion
  • Produced by the liver and stored in the gallbladder
  • Act as emulsifiers to increase lipid droplet surface area
  • Form mixed micelles with fatty acids and monoglycerides
• Pancreatic phospholipase A2 hydrolyzes phospholipids
  • Releases lysophospholipids and fatty acids
  • Important for cell membrane digestion (red blood cells, bacteria)
• Pancreatic cholesterol esterase breaks down cholesterol esters
  • Yields free cholesterol and fatty acids
  • Facilitates cholesterol absorption

Lipid Absorption in the Small Intestine

Mechanisms of Lipid Uptake

• Absorption occurs primarily in the jejunum and ileum
• Mixed micelles transport hydrolyzed lipids to enterocyte brush border
• Fatty acids and monoglycerides diffuse across enterocyte membrane
  • Short and medium-chain fatty acids enter portal circulation directly
  • Long-chain fatty acids require further processing
• Cholesterol absorption involves NPC1L1 transporter
  • Niemann-Pick C1-Like 1 protein facilitates cholesterol uptake
  • Target of cholesterol-lowering drugs (ezetimibe)

Intracellular Processing and Chylomicron Formation

• Re-esterification of fatty acids and monoglycerides in smooth endoplasmic reticulum
  • Forms new triglycerides
  • Process called re-synthesis
• Chylomicron assembly in Golgi apparatus
  • Incorporates newly synthesized triglycerides
  • Includes cholesterol and phospholipids
  • Apolipoprotein B-48 provides structural framework
• Chylomicron exocytosis and transport
  • Released into intercellular space
  • Enter lymphatic system via lacteals
  • Eventually reach bloodstream through thoracic duct

Lipoproteins for Lipid Transport

Lipoprotein Structure and Composition

• Complex particles with hydrophobic core and hydrophilic shell
  • Core contains triglycerides and cholesterol esters
  • Shell composed of phospholipids, free cholesterol, and apolipoproteins
• Apolipoproteins serve multiple functions
  • Provide structural support (ApoB-100, ApoB-48)
  • Enable receptor recognition (ApoE, ApoB-100)
  • Activate or inhibit enzymes (ApoC-II activates lipoprotein lipase)

Lipoprotein Metabolism and Lipid Exchange

• Dynamic processes of lipid exchange between lipoproteins
  • Cholesteryl ester transfer protein (CETP) facilitates lipid transfer
  • Phospholipid transfer protein (PLTP) exchanges phospholipids
• Lipolysis by lipoprotein lipase (LPL)
  • Hydrolyzes triglycerides in chylomicrons and VLDL
  • Releases fatty acids for tissue uptake (adipose tissue, skeletal muscle)
• Receptor-mediated endocytosis
  • LDL receptors recognize ApoB-100 and ApoE
  • Hepatic uptake of remnant lipoproteins via LDL receptor-related protein (LRP)

Lipoprotein Classes and Functions

Triglyceride-Rich Lipoproteins

• Chylomicrons transport dietary triglycerides
  • Largest and least dense lipoproteins
  • Synthesized in intestinal enterocytes
  • Contain ApoB-48 as primary structural protein
• Very-low-density lipoproteins (VLDL) carry endogenous triglycerides
  • Synthesized in the liver
  • Contain ApoB-100 as primary structural protein
  • Precursors to LDL formation

Cholesterol-Rich Lipoproteins

• Low-density lipoproteins (LDL) deliver cholesterol to peripheral tissues
  • Often called "bad cholesterol" due to association with atherosclerosis
  • Contain high proportion of cholesterol and cholesteryl esters
  • Recognized by LDL receptors on cell surfaces
• High-density lipoproteins (HDL) mediate reverse cholesterol transport
  • Remove excess cholesterol from peripheral tissues
  • Deliver cholesterol to liver for excretion or recycling
  • Associated with cardiovascular protection ("good cholesterol")

Intermediate and Specialized Lipoproteins

• Intermediate-density lipoproteins (IDL) form during VLDL metabolism
  • Can be further metabolized to LDL or taken up by the liver
  • Contain both ApoE and ApoB-100
• Lipoprotein(a) [Lp(a)] is a modified LDL particle
  • Contains an additional protein called apolipoprotein(a)
  • Associated with increased cardiovascular risk
  • Levels largely determined by genetic factors