Lipid Digestion and Absorption

Lipid digestion and
absorption
Digestion of dietary lipids
• Diet contains about 60-150 g of fat
– On an average 80 g approximately/day
• Dietary lipids:
– Triacyl glycerol (Triglyceride): 90%

– Cholesteryl esters
– Phospholipids
– Cholesterol
– Free fatty acids
Lipases
• are lipid hydrolyzing enzymes
• Lingual lipase
• Gastric lipase
• Pancreatic lipase & colipase
• Intestinal lipase
• Lipoprotein lipase
• Hormone sensitive lipase etc.
Digestion of lipids
• Lingual lipase: (in the mouth)
– Dorsal surface of tongue (Ebner’s gland)
– Acts on TAG of short and medium chain fatty

acids- Eg. milk fat, butter fat, ghee etc.
• Products are short and medium chain fatty
acids
• pH: 4-6 approximately
• Significant in the case of infants for the

digestion of milk fat
In stomach
• Heat of the stomach is important in
liquidizing dietary lipids
• Emulsification/mixing takes place

aided by gastric contractions
• In the stomach, gastric mucosa
secretes Gastric lipase
• pH optimum 4-6
• Acts on fats of short & medium chain

fatty acids
• Lingual and gastric lipases initiate lipid
digestion by hydrolyzing TAG containing
short & medium chain FA to form
– FFA, & 1,2- diacyl glycerol
• Particularly important during neonatal

period (secretion of HCl is low )
• No emulsification in stomach
– Hence, insignificant in adults
• Both are important for the digestion
of milk fat
• Based on retention time of 2-4 hrs.

about 30% of dietary TAG can be
digested in this time
• The released fatty acids ( short and
medium chain) may be absorbed via
the stomach wall and enter the portal
vein
• Any long chain fatty acids dissolve in

the fat droplets and pass on to the
duodenum
In the intestine
• Pancreatic secretion contains :
– Pancreatic lipase & colipase

– Cholesteryl ester hydrolase
(cholesterol esterase)
– Phospholipase A2
• Stimulation of pancreatic and bile
juice secretion
– Acid chyme from stomach after entering to

duodenum, stimulates secretion of small
peptide hormones from mucosa of lower
duodenum and jejunum (gut endocrine
glands)
• Cholecystokinin (CCK,
pancreozymin)
• Secretin
• Cholcystokinin:
– Acts on gall bladder causing it to contract and

release bile
– Acts on the exocrine cells of the pancreas

causing the release of digestive enzymes
– It also decreases the gastric motility: slower

release of gastric contents to the duodenum
• Secretin: secreted in response to low pH- it
causes the pancreas and liver to release
watery solution rich in bicarbonate
• Bile juice contains: bile salts,
phospholipids and free cholesterol
• Pancreatic secretion contains:

Pancreatic lipase, procolipase,
cholesteryl esterase, phospholipase A2
At the intestine
• Emulsification of Lipids in the small
intestine
• Emulsification is dispersion of lipids into

smaller droplets due to reduction in the
surface tension
• This is accompanied by increase in the

surface area of the lipid droplets
• Emulsification is essential for lipid
digestion
• Process of emulsification occurs by

– Detergent action of bile salts
– Surfactant action of degraded lipids
– Mechanical mixing due to peristalsis
• Bile salts: biological detergents
synthesized from cholesterol
• Primary bile acids: cholic acid and

chenodeoxycholic acids
– Conjugated bile acids: glycocholic acid,

Taurocholic acids; glycochenodeoxycholic
acids and taurochenodeoxycholic acids
• Bile salts: sodium and potassium
salts of conjugated bile acids
• Properties of bile:
– Bile salts have considerable ability to lower

surface tension
– This enables them to emulsify fats in the

intestine and to dissolve fatty acids and
water-insoluble soaps
Mixed micelle formed by bile salts, triacylglycerols and pancreatic
lipase.
• Bile is an important adjunct to
accomplish the digestion and
absorption of fats as well as the
absorption of fat soluble vitamins: A, D,
E, K
• Bile helps in the neutralization of acid

chyme from the stomach
• Pancreatic lipase attacks the primary ester
links of the TAG
– Lipase: acts at the oil water interface of the

finely emulsified lipid droplets formed by
mechanical agitation in the gut in the presence
of lingual lipase, gastric lipase, bile salts,
colipase, PL-A2
Intestinal villi
Intestinal Uptake of Lipids
• In order for the body to make use of dietary lipids,
they must first be absorbed from the small
intestine.
• Since these molecules are oils, they are essentially

insoluble in the aqueous environment of the
intestine. The solubilization (or emulsification)
of dietary lipids is therefore accomplished by
means of bile salts
Pancreatic lipase and colipase
• pH optimum: alkaline range for
all pancreatic enzymes
Pancreatic Lipase with colipase
• The emulsification of dietary fats renders
them accessible to pancreatic lipases and
phospholipase A2
• generate free fatty acids and a mixtures of

mono- and diacylglycerols from dietary
triacylglycerols. Pancreatic lipase degrades
triacylglycerols at the 1 and 3 positions
sequentially to generate 1,2-
diacylglycerols and 2-mono acylglycerols.
Pancreatic Lipase + Colipase
(bile salts, alkaline pH)
• TAG  1,2-DAG  2- MAG
FFA FFA
Isomerase
1 –Monoacyl glycerol
FFA + Glycerol
• Orlistat, an antiobesity drug inhibits gastric
and pancreatic lipases  decreasing fat
absorption  result in loss of weight
• A non hydrolysable analog of TAG

Phospholipase A2
• Phospholipids are degraded at the 2 position
by pancreatic phospholipase A2 releasing a
free fatty acid and the lysophospholipid
• Lysophospholipases can act further on
lysophospholipids to remove fatty acid from
C-1 position
Cholesterol esterase
Cholesterol
Fatty +
acid FFA
Absorption of digested dietary
lipids
• Digested lipid products include:
 2-MAG, FFA, Cholesterol,

lysophospholipids, glycerol
• Absorption mainly occurs through
diffusion into the intestinal
epithelial cells, where the re-
synthesis of triacyglycerol occurs
• Different theories:
– Lipolytic theory by Verzar

– Partition theory by Frazer
– Bergstrom theory
• Verzar theory:
– fats are completely hydrolysed to

glycerol and FFA and later are
absorbed in association with bile
salts
• Frazer theory:
– TAG digestion is partial and not complete
– Then forms emulsion/micelles with bile

salts and absorbed
– Resynthesis of fat in the intestinal

mucosal cell is not necessary for the
entry into circulation
• Bergstrom theory:
– According to this, after absorption of

digested lipids, there will be resynthesis
of TAG in the intestinal mucosal cell
before entering into the circulation
• A most recent and comprehensive one & replaces

other two
Resynthesis of TAG, PL, CE in
the intestinal mucosal cell &
formation of chylomicrons
• Fatty acyl CoA synthetase
• Acyl CoA-monoacyl glycerol acyl
transferase
• Acyl CoA-diacyl glycerol acyl transferase
• Acyl CoA-cholesterol acyl transferase
• Apolipoprotein B-48
• Phospholipids
Acyl CoA synthetase (thiokinase)
• Fatty acid + CoA + ATP  Fatty acyl CoA

+ AMP + PPi
Acyl CoA-mono and di acyl
glycerol acyl transferases
• Acyl transferases-
 2- MAG + fatty acyl CoA  1,2- DAG +

CoA
 1,2-DAG + fatty acyl CoA  TAG + CoA

Acyl transferase
• Lysophospholipid + Acyl CoA  Phospholipid

+ CoA
Acyl CoA-cholesterol acyl
transferase
• Cholesterol + fatty acyl CoA  Cholesterol ester

+ CoA
Enterohepatic circulation
• Bile salts secreted into the intestine are
efficiently reabsorbed (more than 95%)
primarily from the ileum through portal
blood
• Mixture of primary and secondaary bile

acids (deoxy cholic acid & lithocholic
acids)
• Only about 0.5 g is lost in feces
• Cholestyramine, a drug, bind bile acids in

the gut and prevent its reabsorption and
promotes excretion in the feces
– Used in hypercholesterolemia
Disorders
• Malabsorption
• Steatorrhea
• Cystic fibrosis
Malabsorption of lipids
• Steatorrhea
– Increased lipids (fats and fat soluble vitamins,
essential fatty acids etc.) in the feces
– any disturbance in lipid digestion and

absorption
– Shortened bowel
Steatorrhea may be due to
• 1. A defect in the secretion of bile or
pancreatic juice into the intestine.
• 2. Impairment in the lipid absorption by the
intestinal cells
It is commonly seen in disorders associated
with pancreas, biliary obstruction, severe liver
dysfunction etc
• Colipase deficiency: patients suffers from
steatorrhea
– A result of defective Pancreatic lipase activity

• Pancreatic insufficiency
• Cystic fibrosis- mutation in the gene for the

cystic fibrosis transmembrane conductance
regulator (CFTR) protein
– CFTR protein functions as chloride channel on

epithelium
• In Cystic fibrosis decreased hydration of
pancreas results in thickened secretion of
pancreas
– Hence, enzymes of pancreas are not able to

reach the intestine- leading to pancreatic
insufficiency
• Pancreatitis: inflammation of pancreas
• Any severe hepatic dysfunctions (liver

diseases), causing decreased bile secretion
• Obstruction of the biliary tract, decreased

bile flow
• Measurement of serum amylase is used in
the diagnosis of pancreatitis
Celiac disease (Celiac sprue)
• A disease of malabsorption caused by
immune-mediated damage to small
intestine.
• Caused in some individuals as a result of
indigestion of gluten
• Cholesterol gall stones are formed when
liver secretes bile ( containing PLs, bile
acids etc) supersaturated with respect to
cholesterol
Chyluria
• Patients excretes milky urine
• Presence of an abnormal connection

between the urinary tract and the
lymphatic drainage system of the intestine
- so called chylous fistula
Chylothorax
• An abnormal connection between the
pleural space and the lymphatic drainage
of small intestine that results in the
accumulation of milky pleural fluid

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Lipid Digestion and Absorption

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Lipid digestion and

– Triacyl glycerol (Triglyceride): 90%

– Acts on TAG of short and medium chain fatty

• pH: 4-6 approximately

• Significant in the case of infants for the

• Emulsification/mixing takes place

• Acts on fats of short & medium chain

• Particularly important during neonatal

• Based on retention time of 2-4 hrs.

• Any long chain fatty acids dissolve in

– Pancreatic lipase & colipase

– Acid chyme from stomach after entering to

– Acts on gall bladder causing it to contract and

– Acts on the exocrine cells of the pancreas

– It also decreases the gastric motility: slower

• Pancreatic secretion contains:

• Emulsification is dispersion of lipids into

• This is accompanied by increase in the

• Process of emulsification occurs by

• Primary bile acids: cholic acid and

– Conjugated bile acids: glycocholic acid,

– Bile salts have considerable ability to lower

– This enables them to emulsify fats in the

• Bile helps in the neutralization of acid

– Lipase: acts at the oil water interface of the

• Since these molecules are oils, they are essentially

• generate free fatty acids and a mixtures of

• A non hydrolysable analog of TAG

 2-MAG, FFA, Cholesterol,

– Lipolytic theory by Verzar

– fats are completely hydrolysed to

– TAG digestion is partial and not complete

– Then forms emulsion/micelles with bile

– Resynthesis of fat in the intestinal

– According to this, after absorption of

• A most recent and comprehensive one & replaces

• Fatty acid + CoA + ATP  Fatty acyl CoA

 2- MAG + fatty acyl CoA  1,2- DAG +

 1,2-DAG + fatty acyl CoA  TAG + CoA

• Lysophospholipid + Acyl CoA  Phospholipid

• Cholesterol + fatty acyl CoA  Cholesterol ester

• Mixture of primary and secondaary bile

• Cholestyramine, a drug, bind bile acids in

– any disturbance in lipid digestion and

– A result of defective Pancreatic lipase activity

• Cystic fibrosis- mutation in the gene for the

– CFTR protein functions as chloride channel on

– Hence, enzymes of pancreas are not able to

• Any severe hepatic dysfunctions (liver

• Obstruction of the biliary tract, decreased

• Presence of an abnormal connection

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