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

• 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

Glycerol + 3 FA’s Triglyceride + 3 H20

H

H--C--OH

H--C--OH

H--C--OH

H

O

HO-C-R

O

HO-C-R

O

HO-C-R

+

H O

H--C--O--C--

O

H--C--O--C--

O

H--C--O--C--

H

R + H2O

R + H20

R + H20

Text art 06_02

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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

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

omega end alpha end

H H H H H H H H H H H H H H H H H O

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

Fatty Acid Nomenclature

Configuration/Shape

• cis versus trans

Common Fatty AcidsNAME STRUCTURE PROPERTIES Acetic acid 2:0 Formed from glucose and amino acid degradation Propionic acid 3:0 Formed from odd-chain fatty acids and branched-

chain amino acids Butyric acid 4:0 Found in cows’ milk and butter Decanoic acid 10:0 Major fatty acid in milk triglycerides Palmitic acid 16:0 End product of fatty acid synthesis in most tissues Stearic acid 18:0 Major fatty acid in gangliosides Oleic acid 18:1 (∆9) Lowers plasma LDL when substituted for

saturated fatty acids Linoleic acid 18:2 (∆9,12) Essential fatty acid and precursor of Arachidonic

acid Linolenic acid 18:3 (∆9,12,15) Essential fatty acid Arachidonic 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

• Intake has increased dramatically – Found in margarine, cookies, potato chips, snack

chips, onion rings

• Current intake is~3% of total kcals

risk for heart disease

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

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Essential Fatty Acid Needs

• Adequate Intake– Approximately 2-4 Tablespoons daily

• Deficiency– Unlikely

• Toxicity– No upper level set

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 intake of ~2 servings of fish/wk– Shellfish

– 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:– 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

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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

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

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• 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”

EmulsificationEmulsification

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

• High saturated fat diet

• Diet high in trans fatty acids

• Low fiber diet

• 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• 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 dietReplacing saturated fats with Mono - unsaturated fatsExercise

45 minutes 4 times a weekLosing excess weight, if overweight

Moderateoderate 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

• 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

• 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 Optimal 100-129 Near optimal 130-159 Borderline high 160-189 High >190 Very high Total Cholesterol <200 Desirable 200-239 Borderline high >240 High HDL Cholesterol <40 Low >60 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

• Total Fat 25-35% of total kcals

• SFA <7% of total kcals

• MUFA Up to 20% “ “

• PUFA Up to 10% “ “

• CHO 50-60% of “ “

• Protein 10-20% of “ “

• Cholesterol <200 mg/d

• Fiber 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