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Chapter 6: Lipids
Properties of Lipids
• Do not readily dissolve in water
• Fats are solid at room temperature
• Oils are liquid at room temperature
Functions of Lipids
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Provide energy
Satiety
Flavor and mouth feel
Insulation
Protect internal organs
Transport fat-soluble vitamins
Efficient storage of energy
– 80% lipid, 20% protein and water
Triglycerides
• Triglycerides are the main form of lipids in
food and body (storage)
• Energy dense (9 kcal /g)
Triglycerides
H
O
H--C--OH
HO-C-R
H
H--C--O--C-- R + H2O
O
H--C--OH
+
HO-C-R
O
H--C--O--C-- R + H20
O
H--C--OH
HO-C-R
H
Glycerol
O
O
H--C--O--C-- R + H20
H
+
3 FA’s
Triglyceride + 3 H20
Text art 06_02
Structure
• Esterification
– Joining 3 fatty acids to a glycerol unit
• De-esterification
– Release of fatty acids-results in free fatty acids
• Diglyceride
– Loss of one fatty acid
• Monoglyceride
– Loss of two fatty acids
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Structure of Fatty Acids
• Fatty acids
– Function is dependent on:
• Length
• Degree of saturation
• Location of double bonds
• Configuration/Shape
– Glycerol backbone
Fatty Acid Chain Length
• Long chain FA: > 12 Carbons
– Predominant in food (meats, fish)
• Medium chain FA: 6 - 10 Carbons
– Account for ~4-10% of all FA
• Short chain FA: < 6 Carbons
– Found in dairy products
Saturated Fatty Acid
Monounsaturated Fatty Acid
Polyunsaturated Fatty Acid
Location of Double Bonds
• Omega System
– Double bond closest to omega (methyl) end
– Omega: refers to the last carbon (methyl
group)
– Omega 6 vs Omega 3 fatty acids
• Delta (alpha) System
– Uses the carboxyl end and indicates location
for all double bonds
Fatty Acid Structure
H H H H H H H H H H H H H H H HHO
H-C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C-C-OH
H H H H H H H H H H H H H H H H H
omega end
end
alpha
Fatty Acid Nomenclature
Configuration/Shape
• cis versus trans
Common Fatty Acids
NAME
Acetic acid
Propionic acid
Butyric acid
Decanoic acid
Palmitic acid
Stearic acid
Oleic acid
Linoleic acid
Linolenic acid
Arachidonic acid
STRUCTURE
2:0
3:0
PROPERTIES
Formed from glucose and amino acid degradation
Formed from odd-chain fatty acids and branchedchain amino acids
4:0
Found in cows’ milk and butter
10:0
Major fatty acid in milk triglycerides
16:0
End product of fatty acid synthesis in most tissues
18:0
Major fatty acid in gangliosides
18:1 (∆9)
Lowers plasma LDL when substituted for
saturated fatty acids
18:2 (∆9,12)
Essential fatty acid and precursor of Arachidonic
acid
18:3 (∆9,12,15) Essential fatty acid
20:4 (∆5,8,11,14) Precursor of most eicosanoids
Saturated Fatty Acids
• Fatty acids with no double bonds
• Solid at room temperature
• Animal fats:
– Dairy: cheeses, ice cream, whole milk
– Meat: beef, pork, lamb,
– Plant/tropical oils (cottonseed, coconut)
• Stearic, lauric, myristic, palmitic
Saturated Fatty Acid
Trans Fatty Acids
• Essentially a saturated fat
• Raise LDL
• Lower HDL
risk for heart disease
• Intake has increased dramatically
– Found in margarine, cookies, potato chips, snack
chips, onion rings
• Current intake is~3% of total kcals
Hydrogenation of Fatty Acids
• Process used to solidify an oil
• Addition of hydrogen to an unsaturated fatty acid
(eliminating the double bond—making it into a
saturated fatty acid)
• Trans fatty acids are a by product of
hydrogenation
• How can we limit intake of these?
Figure 06_07
Trans Fatty Acid
Food Labels
• % Daily Value on Nutrition Facts label is sum of
trans and saturated fatty acids
• Quantity of trans fatty acids
• “Trans fat free” has no more than 0.5 g each of
trans or saturated fat
•
Read the food label and look for hydrogenated or
partially hydrogenated oils, or trans fatty acids
Trans Fatty Acids
Monounsaturated Fatty Acids
• One double bond
• Oleic acid (Omega 9)
• Olive oil, canola oil, nuts
• Rate of CHD low in Mediterranean countries
where diet is rich in olive oil
• Diet high in MUFA equivalent to low-fat diet in ↓
LDL-C, but does not ↓ HDL-C
Monounsaturated Fatty Acid
Polyunsaturated Fatty Acids
• 2 or more double bonds
• Provides essential fatty acids (EFAs)
– Omega 3
– Omega 6
• Properties differ between these EFAs
Polyunsaturated Fatty Acid
Figure 06_11
Essential Fatty Acids
• Polyunsaturated fatty acids
• Body can only make double bonds after
the 9th carbon from the omega end
•
• Needed for
– immune function
– vision
– cell membranes
– production of hormone-like compounds
Essential Fatty Acid Needs
• Adequate Intake
– Approximately 2-4 Tablespoons daily
• Deficiency
– Unlikely
• Toxicity
– No upper level set
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Omega-3 Fatty Acids
• Linolenic acid (α-linolenic acid)
• Forms eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA)
• Metabolized to form eicosanoids
Omega-3 Fatty Acids
• Consumption of large amounts of omega-3 fatty
acids decreases the ability of blood to clot
• May:
– Prevent stroke and heart attacks caused by
clots (thrombosis)
– Reduce risk of stroke caused by blood clots
– Help some chronic inflammatory conditions
• Asthma, rheumatoid arthritis, psoriasis
Omega-3 Fatty Acids
– Recommend
– Shellfish
intake of ~2 servings of fish/wk
– Cold water/fatty fish (salmon, mackerel, sardines, tuna)
• Consumption of canola or olive oil vs. other plant oils
• Flaxseed oil
– 2 tbsp per day
• Fish oil capsules
– 900 mg per day
– Avoid: if have a history of bleeding
disorder, on blood thinners
Omega-6 Fatty Acids
• Linoleic acid
• Forms arachidonic acid
• Metabolized to eicosanoids
• Found in vegetable oils
– Corn, sunflower, safflower, soybean oils,
nuts, seeds, wheat germ
• Only need ~ 1 tablespoon a day
Eicosanoids
• A group of hormone-like compounds
• By-pass the blood stream and work in the area of
origin
• Regulators of:
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Blood pressure
Clotting
Immune responses
Inflammatory responses
Stomach secretions
• Prostaglandins, thromboxanes, leukotrienes,
prostacyclins, lipoxins
Eicosanoids Have Different
Effects
• Omega-3 eicosanoids, DHA, EPA
– ↓ blood clotting
– ↓ inflammatory responses
– Reduce heart attack
– Excess may cause hemorrhagic stroke
• Omega-6 eicosanoids; Arachidonic acid
– ↑blood clotting
– ↑ inflammatory responses
• Eicosanoids have different effects on
different tissues
American Heart Association
Recommendations
• Total fat:
<30% of total calories
• Saturated fat:
<10% of total calories
• Monounsaturated fat: 10% of total calories
• Polyunsaturated fat:
10% of total calories
• Cholesterol:
<300 mg/day
Phospholipids
• Hydrophobic and Hydrophillic Ends
• Functions
– Component of cell membranes
– Eicosanoid synthesis
– Emulsifier
• Allows fats/lipids to be dispersed in water
– Bile acids
• Sources
– Synthesized by the body as needed
– Built on a glycerol backbone
• At least one fatty acid replaced with phosphorus compound
– Food: egg yolks (lecithin), wheat germ and peanuts
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Emulsifier
Hydrophilic end
(attracts water)
Hydrophobic end
(attracts lipid)
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Sterols
• Multi-ringed structure, most known is
cholesterol
• Functions
– Bile acids, cell membranes
– Precursor of steroid hormones, sex
hormones, adrenal hormones, Vitamin D
• Sources
– Synthesized by the liver
– Food: animal origin
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Lipid Digestion
• Mouth
– Lingual lipase (inactive until reaches stomach)
• Stomach
– Gastric lipase (digests primarily SCFAs)
– Muscular contractions mix fat with digestive
enzymes
– Fats generally remain in stomach 2-4 hours
Lipid Digestion
• Small intestine
– Cholecystokinin (CCK) and Secretin
• Released due to presence of fat in duodenum
• CCK stimulates release of
– Pancreatic lipase
– Bile (to help emulsify fat)
• Secretin stimulates release of
– Bicarbonate
» Raises pH for activation of lipases
Bile
• Composed of bile acids, bile pigments,
phospholipids (lecithin)
• Synthesized from cholesterol in the liver
• Function is to emulsify fat
– Allows fat to be suspended in watery digestive juices
– Large fat globules broken down to smaller ones,
surface area for lipase action increases
– Micelles are formed
Bile
• Once used for emulsification, can go through 1
of 2 routes:
– Reabsorbed in small intestine and recycled
– Binds to fiber in large intestine and excreted
• This is how fiber (in particular soluble fiber) helps
lower blood cholesterol levels
Enterohepatic Circulation
End Products of Lipid Digestion
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Glycerol
Fatty acids
Cholesterol
Lecithin
Lipid Absorption
• Micelles
– Emulsified fat droplets
– Absorbed across intestinal mucosal cells by diffusion
• Distal duodenum, jejunum
• End products of dietary lipid digestion
– Repackaged into chylomicrons
– Released into lymph system
• Bile salts absorbed in the ileum
– Returned to liver via portal vein to be reused
– “Enterohepatic circulation”
Emulsification
Lipid Transport
• Water (blood) and oil (fat) are
incompatible
• Unique system of fat transportation
needed for lipids to travel in
bloodstream
Lipid Transport
• Lipoproteins
– Transport lipids through bloodstream
– Composed of:
• Triglycerides, protein, phospholipids, cholesterol
– 4 different types
• Chylomicrons
• VLDL (Very-low density lipoprotein)
• LDL (Low density lipoprotein)
• HDL (High density lipoprotein)
Lipoprotein
Chylomicrons
• Large in size
• Triglyceride–rich (80-90% TG)
• Transport dietary (exogenous) fat to cells
– High blood concentrations following a meal
• Transported via lymph system, enter
bloodstream at thoracic duct
Chylomicrons
• Lipoprotein lipase (LPL) breaks down TGs in chylos
• Fatty acids are absorbed by cells (muscle, adipose,
etc.)
• Chylomicron remnants removed by the liver, broken
down, and repackaged into VLDL
– At this point, fats are considered ENDOGENOUS
• 2-10 hours to clear from bloodstream
Dietary Fat Absorption
Very-Low Density Lipoproteins
• Triglyceride-rich (55-65%)
• Transports endogenous fats to cells
– Lipids synthesized in liver
• Released from liver into bloodstream
Very-Low Density Lipoproteins
• Lipoprotein lipase (LPL) breaks down TGs in VLDL
• Fatty acids are absorbed by cells (muscle, adipose,
etc.)
• VLDL remnants are removed by liver, broken down, and
repackaged into LDL
• 10-12 hours to clear from bloodstream
Low Density Lipoproteins
• Cholesterol-rich (45%)
• Transports cholesterol synthesized by liver
• Removed from bloodstream via receptors
(or scavenger pathway)
– Receptors down-regulated with high saturated/trans
fatty acid diet
• 2-3 days to clear from bloodstream
Low Density Lipoproteins
Optimal <100 mg/dl
Factors that raise LDL
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High saturated fat diet
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Diet high in trans fatty acids
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Low fiber diet
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Sedentary lifestyle
High Density Lipoproteins
• Protein rich (45-50%)
• Synthesized by liver and intestine
• Picks up cholesterol from dying cells and
other sources
• Transfer cholesterol to other lipoproteins
for transport to liver for excretion
• HDL can also transfer directly back to the
liver
Benefits of High HDL
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Removes cholesterol from blood
May block oxidation of LDL
Reduces risk of heart disease
Pre-menopausal women have higher HDL
High Density Lipoproteins
Desirable >60 mg/dl
Factors that raise HDL
Low saturated fat diet
Replacing saturated fats with Mono - unsaturated
fats
Exercise
45 minutes 4 times a week
Losing excess weight, if overweight
Moderate amount of alcohol
Lipoproteins
Composition of Lipoproteins
Metabolism of Lipids
• Fatty acids, monoglycerides and other lipids
taken up by tissue cells
• Can be used in 1 of 4 ways:
– Immediate source of energy
– Energy storage (adipose)
– Incorporation into cell membranes
– Used as raw material for synthesis of
essential compounds (cholesterol)
Lipids as an Energy Source
• Hormone sensitive lipase (HSL)
– Enzyme found in liver and adipose tissue
– Key enzyme for lipolysis of stored fat
– Insulin inhibits HSL (inhibits lipolysis)
– Glucagon activates HSL (leads to lipolysis)
Lipids as Stored Energy
• Unlimited capacity for fat storage
• Lipoprotein lipase (LPL)
– Located in adipose and muscle cells
– Facilitates uptake of FA from blood
– Excess energy intake
•  LPL synthesis
•  fat stored in adipose
Health Implications of Fat
• Cardiovascular disease
– Major cause of morbidity and mortality in US
– >500,000 people die every year
– ~1.5 million Americans have a heart attack every year
• Obesity
– Fat is a concentrated source of calories
– Abdominal fat associated with  risk for DM and HTN
• Cancer
– High fat diet associated with certain forms of cancer
Heart Disease
• Cardiovascular Disease (CVD)
– Disease of the heart and blood vessels
• Coronary Heart Disease (CHD)
– Damage that occurs when blood vessels carrying
blood to the heart (the coronary arteries) become
narrow and occluded
– Leading cause of death in US
• Myocardial infarction (MI)
– Accounts for ~50% of CVD deaths
– Major underlying cause is atherosclerosis
Development of CHD
• When blood flow via coronary arteries is interrupted
• Heart attack (myocardial infarction) may result leading to
– Irreversible damage to heart muscle
– Irregular heart beat or stopped heartbeat
– 25% of people do not survive their 1st MI
• Cerebrovascular accident (CVA) or stroke
– When blood flow to part of brain is interrupted causing
part of brain to die
Myocardial Infarction (MI)
Signs of a Heart Attack
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Intense, prolonged chest pain
Shortness of breath
Sweating
Nausea and vomiting
Dizziness
Weakness
Jaw, neck, shoulder pain
Irregular heartbeat
Risk Factors for Heart Disease
Modifiable
• Smoking
• Hyperlipidemia
– Total Chol >200 mg/dL
– Low HDL-C <35 mg/dL
– Hight LDL-C
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Obesity
HTN
Physical Inactivity
Diabetes Mellitus
Non-Modifiable
• Age
– Male >45
– Female >55
• Male gender
• Family history of CHD
Other Risk Factors
• Serum Homocysteine
– Amino acid
– High level in blood associated with increased
risk of MI
– Causes damage to blood vessel wall
• Reduce blood level by:
– Increasing folate, B6 and B12 intake
• Fruits, vegetables, etc.
Other Risk Factors
• C-Reactive Protein (CRP)
– Acute phase protein that increases during systemic
inflammation
– Levels in blood increase during inflammation
– Biochemical marker for CVD
National Heart Lung and Blood Institute,
Adult Treatment Panel III Guidelines for
CHD (2001)
LDL Cholesterol
<100
100-129
130-159
160-189
>190
Total Cholesterol
<200
200-239
>240
HDL Cholesterol
<40
>60
Optimal
Near optimal
Borderline high
High
Very high
Desirable
Borderline high
High
Low
High
Reduce Your Risk
(Primary Prevention)
• ↓ dietary saturated fat, trans fatty acid, and
cholesterol
• ↑ MUFA and PUFA to recommended amounts
• ↑ dietary fiber
• Maintain healthy weight
• Don’t smoke
• Alcohol in moderation
• Folate intake
• Low glycemic index load
Secondary Prevention
(After a Heart Attack)
• Primary prevention techniques
• Medication
• Megadoses of vitamin E (400-800 IU/day)
Therapeutic Lifestyle Changes
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Total Fat
SFA
MUFA
PUFA
CHO
Protein
Cholesterol
Fiber
25-35% of total kcals
<7% of total kcals
Up to 20% “
“
Up to 10% “
“
50-60% of “
“
10-20% of “
“
<200 mg/d
20-30 g/d
Therapeutic Lifestyle Changes
• Other recommendations:
– Plant stanols/sterols
• 2 g/d
– Kcals
• To maintain optimal weight, prevent weight gain
– Physical activity
• Expend at least 200 kcal/d
Medical Therapy
• Statin drugs
– Lipitor, Zocor, Mevacor, etc.
– Successful in reducing blood cholesterol
• Benecol and Take Control
– Plant stanol ester
– Cholesterol-lowering effect
– Compete with cholesterol in the micelle and reduce
absorption of dietary cholesterol
Medical Therapy
• Surgical Intervention
– Angioplasty
– Coronary Artery Bypass Graft (CABG)
Angioplasty
Stent placement
CABG surgery