LIPID DIGESTION
Anson Lowe
October 02, 2015

Understand the digestion of lipids from the mouth to the
bloodstream
Cholesterol absorption

Triglycerides; cholesterol; absorption

Lipids
Elephant seal milk - 55% fat
Half and half - 10% fat
Human breast milk - 5% fat
Birthweight = 60 lbs.
30 days old = 250 lbs.
speed = 60-100 mph
distance 20,000 miles
Migrates 25,000 miles/year
Non-stop 2,400 miles
USGS
Ruby-Throated Hummingbird

Migrates across the Gulf of Mexico - 500 mi

Time ~ 10-20 hrs

Speed = 50 mi/hr

Bird weight 3-4 grams (little more than a penny)

O2 consumption: 250 ml/hr

Power = (0.25 L O2/hr)(4.82 kcal/liter O2) =1.2 kcal/hr or 12 kcal for a 10hr trip

Fat required = 12kcal, 9kcal/gm=1.3 gm

Fuel weight if carbohydrates used 4kcal/gm = 3.0 gm
Oliver Pearson. The metabolism of hummingbirds. Scientific American, January, 1953, p. 69-72.
Lipid Source
Source
Diet
75%
Bile
10%
Sloughed Cells
15%
Dietary Source

Triglycerides make up 95% of dietary lipids
Cholesterol
Stryer, Biochemistry, 5th ed.
Phospholipids
Salivary Glands and Stomach

Initiation of lipid digestion with salivary and
gastric lipase
◦ Results in the liberation of some free fatty acids,
which stimulates CCK and secretin secretion.

Mixing and emulsifying lipids into small
droplets.
Duodenum
CCK and Secretin results in the secretion of bile
and pancreatic secretions into the intestine.
 Bile Salts incorporate triglycerides and
cholesterol into micelles.

Pancreatic Lipase/Colipase

Lipase cleaves the 1and 3 fatty acyl chains off
of triglyceride
◦ Colipase facilitates triglyceride hydrolysis by keeping
lipase at the interface with the lipid droplet
◦ Colipase is activated by trypsin
Orlistat
Used for the treatment of obesity
 Covalently binds to a serine in the active site of
gastric and pancreatic lipase
 Causes fat malabsorption
 Adverse effects

06/07/2007
PAL Announces First Bitter Pill Award of
2007 to GlaxoSmithKline: 'With Allies Like
This, Who Needs Enemas?’ Award
Bile salt-dependent lipase
Produced in the pancreas and mammary gland
 Cleaves carboxy-ester bond of triglycerides and
cholesterol esters

◦ Can completely hydrolyze triglycerides to glycerol
and fatty acids
◦ Is an important source for lipase in neonates with
immature pancreatic function.
Unstirred Water Layer
Long chain fatty acid absorption
Previously thought that long chain (C>12) were only passively absorbed
by the intestine.
 A series of protein transporters have been described that transport fatty
acids into cells (FATP).

◦ FATP4 is highly expressed in the intestine
◦ A knockout for FATP4 is lethal
◦ Heterozygotes for FATP4 mutation have decreased fatty acid absorption
Dietary Lipid Uptake
Fatty Acid Binding Protein
Isoforms are present in many cells (liver,
muscle and intestine)
 FABP2 is highly expressed in the intestine

◦ Cytosolic carrier for long chain fatty acids
Apolipoprotein B
240 kDa protein
 forms amphipathic spherical shell around the
fat globule

◦ solubilizes hydrophobic lipids
◦ contains cell targeting signals
Sci Rep. 2011;1:139
Dietary Lipid Uptake
http://www.elu.sgul.ac.uk/rehash/guest/scorm/294/package/content/liver_lipoprotein.html
Abetalipoproteinemia

Mutations in microsomal triglyceride transfer
protein (MTP)
◦ Failure to thrive, fat malabsorption, retinal
pigmentation, coagulation disorders

Pathology reveal enterocyte engorgement with
lipid.
Sidler: Arch Pediatr Adolesc Med, 151(12):1265-1266
Abetalipoproteinemia-Therapy

Administration of medium chain triglycerides
(C6-C12).
◦ Are more water soluble than long chain FAs
◦ Can be absorbed into enterocytes without bile acids
◦ Incorporation into chylomicrons is not necessary
 Is released directly into the portal circulation
Sterol Absorption
Animal derived sterols (cholesterol) are
preferentially absorbed over plant sterols
(sitosterol, brassicasterol, and avanesterol)
 A specific protein, has been found that
specifically transports cholesterol

NPC1L1

Gene was found via a genomics-bioinformatics
approach
◦
◦
◦
◦

signal peptide
transmembrane domain
N-glycosylation site
cholesterol interacting site/sterol sensing domain
Resulted in one candidate gene
Altmann et al. Science, Vol 303, 1201-1204 (2004)
Altmann et al. Science, Vol 303, 1201-1204 (2004)
Altmann et al. Science, Vol 303, 1201-1204 (2004)
J.W. Clader, J. Med. Chem., 47, 1 -9 (2004)
Sterol Efflux
Animal derived sterols (cholesterol) are preferentially absorbed over
plant sterols (sitosterol, brassicasterol, and avanesterol)
 ABCG5 and ABCG8 form a heterodimer and are responsible for intestinal
efflux and hepatocyte excretion of cholesterol.

◦ Responsible for cholesterol secretion into the bile caniliculus
Small, D.M., PNAS (2003) 100:4-6
J. Clin. Invest. 110 :671-680 (2002)
Malabsorption
Loss of lumenal digestion
(effects on pancreatic enzymes)

◦
◦
◦
◦
chronic pancreatitis
blocked pancreatic duct
absence of bile salts
wrong pH
Malabsorption

Loss of mucosal absorption
(Loss of mucosal surface)
◦ celiac sprue
 autoimmune process initiated by gliadin derived from glutin
◦ whipple disease
 Tropheryma whippelii
◦ tropical sprue
◦ Crohn’s disease
Celiac Sprue
Small Intestine Surface Area

Normal ~300 m2

Tube 2 cm in diameter and 4 meters long
~.25 m2
Malabsorption

Loss of mucosal digestion and absorption
(Loss of mucosal surface)
◦ celiac sprue
 autoimmune process initiated by gliadin derived from glutin
◦ whipple disease
 Tropheryma whippelii
◦ tropical sprue
◦ Crohn’s disease
Malabsorption

Loss of mucosal digestion
(Loss of enzymatic activity or transport)
◦ lactose intolerance