Lipids

Question 1

Lipid

Characteristics

Answer 1

Triacylglycerols, phospholipids, and cholesterol.

Caloric content mainly in fatty acids.

Metabolized to acetyl CoA to generate ATP.

Nutritionally categorized into 3 groups:

1. Saturated (SAT)
   
   • warm blooded animals
2. Monounsaturated (MUFA)
3. Polyunsaturated (PUFA)
   
   • plants grown in cooler climates
   • cold water fish

Question 2

Trans Fatty Acids

Answer 2

1. Sources:
   
   • Modest amount in meat and dairy products due to bacterial fermentation
   • Significant amount in partially hydrogenated oils (PHOs)
     
     • Formed via catalytic hydrogenation of polyunsaturated vegetable oils
   • Baked and fried foods
2. Effects:
   
   • ↑ plasma cholesterol
   • ↑ LDL
   • ↓ HDL
   • ↑ risk of CAD

Question 3

Essential Fatty Acids

Answer 3

Linoleic acid (18:2 𝜔-6)

𝛼-Linolenic (18:3 𝜔-3)

• Dietary recommendations:
  
  • EFAs should be ≥ 1% total energy
  • During pregnancy or lactation, ≥ 3% total energy (3 en%)
    
    • Especially 𝛼-Linolenic (18:3 𝜔-3)
    • Accounts for most of the EFAs in brain
• Further desaturation and elongation forms:
  
  • arachidonic acid
  • eicosapentaenoic acid (EPA)
  • docosahexaenoic acid (DHA)

Question 4

Essential Fatty Acid (EFA)

Deficiency

Answer 4

All cells require EFAs for proper function.

Deficiency results in numerous symptoms including scaly and dry skin.

Condition quite rare.

Normally, EFA → eicosanoids (20:4) ⇒ a tetraene.

With deficiency, oleate → closest product (20:3 𝜔-9) ⇒ a triene.

Triene/Tetraene ratio above 0.2 suggestive of EFA deficiency.

EFA deficiency associated with:

• geriatric patients with poor diets
  
  • especially those with PAD
• fat malabsorption syndromes
  
  • especially after surgical bowel resections
• prolonged parenteral alimentation when formula EFA deficient

Question 5

Dietary Lipids

Answer 5

• Triglycerides are 90% of dietary lipids
  
  • digestion/absorption virtually complete
• Phospholipids important for digestive process
  
  • some secreted in bile along with bile acids
• Sterols tag along
  
  • RDA < 300 mg/day
  • normal intake 200-600 mg/day
  • digestion/absorption incomplete
  • endogenous secreted in bile

Question 6

Lipid Digestion

Answer 6

1. Lingual lipase (oral phase) and gastric esterases (gastric phase) start digestion.
   
   • Active at low pH of the stomach
     
     • Minimal in newborns due to poor gastric acid secretion
   • Minimal effect on LCFA esters
2. Intestinal lipolysis ⇒ hydrolysis of fatty acid esters
   
   • Triglycerides → FFA + diglycerides → monoglycerides (2-MG) + FFA
     
     • Pancreatic lipase + colipase mainly
       
       • Colipase binds lipase + TAG droplet
       • Displaces bile salts + phospholipids
       • Allows lipase to work at max rate
     • Intestinal lipases help
     • Max activity @ pH > 7
   • Phospholipids → FFA + other products
     
     • Phospholipase
   • Cholesteryl oleate → cholesterol + oleic acid
     
     • Esterase (Cholesterol ester hydrolase)
       
       • Activated by bile salts
3. Bile salts, phospholipids, FFA, 2-MG, sterols, and other lipids incorporated into mixed micelles.
4. Mixed micelles brought to enterocytes for absorption.

Question 7

Lipid Absorption

Answer 7

1. Mixed micelles brought to enterocytes
2. SCFA and MCFA absorbed directly into blood via portal vein
3. LCFA + apolipoprotins form chylomicrons
4. ​ Chylomicrons absorbed via intestinal lymphatics ⇒ thoracic duct
5. Transported in the blood as part of plasma lipoproteins
   
   • Chylomicrons, VLDL, LDL, HDL

Question 8

Sterol Absorption

Answer 8

• Cholesterol esters must be de-esterified by pancreactic cholesterol esterase to be absorbed
  
  • Includes dietary sterols and endogenous cholesterol from bile
  • Rate of hydrolysis much less than TAGs
• Intestinal free sterols (mainly cholesterol) only absorbed after solubilization in bile salt micelles
  
  • Overall absorption incomplete
  • 2/3 dietary cholesterol excreted in feces
  • Increased dietary intake ⇒ ↑ plasma cholesterol levels
    
    • large individual variation
  • Unexplained specificity of sterol absorption
    
    • only ~ 5% of plant sterols absorbed (ex. 𝛽-sitosterol)
    • high intake of dietary plant sterols interferes with cholesterol absorption

Question 9

𝛽-sitosterolemia

Answer 9

• Rare genetic storage disease
• ~ 1/3 dietary sitosterols are absorbed (plant sterol)
• 𝛽-sitosterol deposits found in many tissues & tendon xanthomas
• plasma cholesterol levels normal

Question 10

Malabsorption Syndromes

Answer 10

Effects:

• Serious nutritional consequences
• Fat-soluble vitamin deficiency
• Steatorrhea
• Interferes with divalent cation absorption (Ca²⁺, Mg²⁺, Zn²⁺)
  
  • unabsorbed fat digestion products form metal soaps with cations
  • because Ca²⁺ bound to FAs, plant oxalate absorption ↑
    
    • major source of kidney stones

Treatment

• Remove most dietary fats
• Replace with medium chain triglycerides (MCT)
  
  • more readily digested
  • can be absorbed without hydrolysis by pancreatic lipase
  • lipolysis releases octanoic and decanoic acids (C8/C10)
    
    • absorbed directly via portal vein
    • improves absorption efficiency

Question 11

Causes of Steatorrhea

Answer 11

1. Pancreatic disease
2. Insufficient bile
   
   • gallbladder or cystic duct obstruction
   • liver dysfunction
3. Loss of large segments of small intestine
4. Damage to intestinal villae
   
   • Celiac disease
   • (non-tropical) Sprue
5. Failure to synthesize chylomicrons
   
   • Abetalipoproteinemia (rare)

Question 12

Celiac Disease

Answer 12

• Fragment of gluten resistent to proteolytic degradation
  
  • found in wheat, oats, and rye but not rice or corn
• Autoimmune response leads to destruction of intestinal villous structure
• Common disorder
  
  • prevalent in Caucasians and East Asians
• 72-hour fecal fat test used for dx
• Symptoms include:
  
  • deficiency of lipid soluble proteins
  • steatorrhea
  • lactose intolerance
  • hypocalcemia
  • weight loss

Question 13

Cystic Fibrosis

&

Malabsorption

Answer 13

• Cystic fibrosis results in impaired salt and water transport due to CFTR channal dysfunction
• Secondary conditions include:
  
  • Exocrine pancreatic insufficiency (PI) in 90% of CF patients
    
    • Results in subsequent fat malabsorption by 1 year of age
    • Detected by:
      
      • 72-hr fecal fat balance study
      • fecal elastase immunosorbent assay
  • CF-related diabetes (CFRD)
  • distal intestinal obstruction syndrome (DIOS)
  • various hepatobiliary diseases
    
    • ​cholelithiasis
    • fibrosis
    • cirrhosis
• Nutritional considerations:
  
  • pancreatic enzyme replacement therapy (PERT)
    
    • attempts to stimulate pancreatic enzyme release
  • lipase deficiency of > 10% normal results in fat-soluble vitamin malabsorption
    
    • ​steatorrhea
    • poor growth
  • may require gastrostomy tubes for feeding
  • nutritional conseling
    
    • caloric intake of 120-150% of normal for age and gender
    • 40% of diet from fat intake
  • female CF patients with PI have increased BEE during puberty
    
    • requires special nutritional attention

Question 14

Fats & Atherosclerosis

Answer 14

• ↑ dietary fat and cholesterol ⇒ ↑ atherosclerosis
  
  • dietary fat most important
    
    • main source of cholesterol synthesized from FA metabolites not dietary sterols
  • foods with high cholesterol but low fat have little effect on lipid profile (ex. shrimp)
• Manifestations of diet effect
  
  • ∆ lipoprotein profile
    
    • ↑ LDL & ↓ HDL
  • ∆ susceptibility to thrombosis
• Effects on fatty acid composition by dietary fats:
  
  • SAT & trans-unsaturated FA more atherogenic
  • PUFA & MUFA (mainly oleic acid) less atherogenic
    
    • diets analyzed via P/S ratio (PUFA:SAT)
  • 𝜔-3 PUFA (fish oils) most antiatherogenic

Question 15

American Heart Association

Dietary Recommendations

Answer 15

1. Overall healthy eating pattern
   
   • balanced diet from all major food groups
   • more fruits, vegetables, grains
   • fish > meat
2. Healthy body weight
3. Desirable cholesterol level
   
   • total blood cholesterol > 200 mg/dl risk factor for CAD
   • total blood cholesterol > 240 mg/dl requires vigorous intervention
4. Desirable BP level
5. Limit trans fats
   
   • hard margarines worse than soft

AHA does not recommend antioxidant supplements, very low fat diets, or 𝜔-3 supplements currently.

Question 16

Mediterranean Diet

Answer 16

• Mediterranean diet emphasizes:
  
  • Eat primarily plant-based foods
    
    • fruits and vegetables, whole grains, legumes and nuts
  • Replace butter with healthy fats like olive oil and canola oil
  • Use herbs and spices instead of salt to flavor foods
  • Limit red meat
  • Eating fish and poultry at least twice a week
  • Enjoying meals with family and friends
  • Drinking red wine in moderation (optional)
  • Getting plenty of exercise
• Benefits:
  
  • reduces the risk of heart disease
  • reduces oxidized LDL levels
  • decreases overall mortality
  • reduced incidence of cancers, Alzheimers, and Parkinsons
• Seven Countries Study:
  
  • Showed serum cholesterol, BP, DM, and smoking are universal risk factors for CAD
  • Mediterranean diet associated with:
    
    • lower rates of CAD
    • lower all-cause mortality
    • postponed cognitive decline
    • decreased risk of depression