Lipid metabolism

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39 Terms

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Fat percentage of daily energy

  • 40% of daily energy

  • ~80-100 grams per day

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Three types of dietary lipids

  1. Triglycerides (95%) → most important

  2. Phospholipids (2%)

  3. Sterols (3%)

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Structure triglycerides

  • Three fatty acids linked via a glycerol molecule

  • Can be different fatty acids

  • Fat if solid at room temperature, oil if liquid at room temperature.

  • Vegetable oils are 100% triglycerides

<ul><li><p>Three fatty acids linked via a glycerol molecule</p></li><li><p>Can be different fatty acids</p></li><li><p>Fat if solid at room temperature, oil if liquid at room temperature. </p></li><li><p>Vegetable oils are 100% triglycerides</p><p></p></li></ul><p></p>
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Fatty acids structures

  • Has a COOH group

  • They can differ in:

    • Chain length

    • Degree of unsaturation

    • Point of saturation (Where is the double bond located?)

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Nomenclature fatty acids

  1. Number of carbons

  2. Number of double bonds

  3. Position of double bonds (for n-designation you count from methyl end + only first double bond, for delta designation you count from carboxyl end and indicates all positions of the double bond)

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Major fatty acids in our diet

  • Palmitic acid (C16:0)

  • Oleic acid (C18:1, monounsaturated) → most important, takes up about 30 - 40% of fatty acids consumed daily

  • Linoleic acid (C18:2)

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What does fatty acid composition determine?

  • firmness

  • stability

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solid/liquid at room temperature

The shorter the fatty acids attached, the lower the melting point of the fat.

  • Solid at room temperature:

    • More saturated

    • Less prone to oxidation

    • e.g. butter

    • more stable

  • Liquid at room temperature:

    • More unsaturated

    • More prone to oxidation

    • e.g. sunflower oil

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Hydrogenation

  • conversion of unsaturated → saturated fatty acids

  • Makes oils more stable and less prone to spoilage

  • It also leads to the conversion of the cis-fatty acids naturally present in foods into trans-fatty acids.

    • Trans-fatty acids have a negative impact on health.

  • Hydrogenation also happens naturally in ruminants → cows and sheep naturally produce trans-fatty acids → present in butter and cheese

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Cis vs trans fatty acids

  • The double bonds within unsaturated fatty acids that are naturally present in foods are in the so called cis configuration → hydrogens on the same side of the double bond.

    • Gives a kink in the molecular shape.

  • Trans configuration means that the two hydrogen atoms are bound to opposite sides of the double bond, which results in a more linear fatty acid. These only form in industrial processing of oils.

    • EXCEPT for conjugated linoleic acid which occurs naturally in dairy.

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Digestion of fat

  • Little fat digestion in mouth (lingual lipase)

  • Little fat digestion in stomach by gastric lipase

  • Most takes place in intestine by pancreatic lipase. Happens in the duodenum, later are absorbed by the bile.

  • Pancreatic lipase breaks down triglycerides into fatty acids in the small intestine.

    • The monoglycerides form a specific structure called a micelle.

  • The enterocytes that are found on the villus take up the micelles and monoglycerides.

  • When they are absorbed they are made back into triglycerides, in a process called re-esterification.

  • They are transported in little droplets called chylomicrons so that they are soluble in the blood.

    • The chylomicrons are deposited into the lacteal vessel which is part of the lymphatic system.

    • Chylomicrons only exist in your blood stream

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Chylomicrons structure

  • Surface coat: unesterified cholesterol, phospholipids, apolipoproteins

  • Core: cholesteryl esters

  • Triglycerides

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What is the fat used for and how does this happen?

  1. Storage (most end up here)

  2. As a form of energy in the muscles

  3. Fatty acid signaling (in the heart)

How this happens?

  • Chylomicrons in the bloodstream encounter the enzyme lipoprotein lipase which can be found on the epithelial cells in the blood vessels

  • Lipoprotein lipase breaks down the triglycerides into fatty acids

  • These fatty acids are then taken up into the tissues and used for one of the three reasons listed above.

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What transports triglycerides?

  • Chylomicrons

  • VLDL = very-low-density lipoproteins.

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What transports cholesterol?

  • Low density lipoproteins

  • High density lipoproteins

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Function of adipose tissue

  • Where excess dietary fat is deposited, storage depot for energy

  • Heat insulation

  • Endocrine function (play a major role in regulation of energy metabolism and food intake)

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Fate of fat in fasted state

  • Stored triglycerides are broken down into single fatty acids and released into the bloodstream to be used by the body.

  • Uses a specific lipase.

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Fat fluctuations

  • Fat release will exceed fat storage at certain times of the day (at night or before meals)

  • Other times fat storage exceeds fat release (after a meal)

  • Over the course of 24 hours, fat storage and release will balance out.

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ATP

  • Battery of the body and is “charged” by breaking down fuels found in triglycerides, carbohydrates and proteins. Heat is released

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Beta-oxidation

  • Inside the mitochondria the fatty acyl-CoA undergoes a series of four enzymatic reactions, collectively known as beta-oxidation, which repeat until the fatty acid is completely broken down.

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Sterols

  • Fat soluble molecules

  • Sterols in foods: cholesterol + plant sterols/stanols (plant version of cholesterol)

  • The main sterol present in animal foods is cholesterol

    • Cholesterol is NOT a nutrient

  • Plants do not contain cholesterol, instead, they contain plant sterols and stanols which resemble cholesterol.

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Plant sterols

  • similar structure

  • Differ from cholesterol at one branch point

  • Only tiny amounts of plant sterols are absorbed, most ingested plant sterols leave the body via the stools

  • They inhibit cholesterol absorption and cholesterol levels in the blood to a maximum of 10%

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Cholesterol levels in the blood

  • <5.0 mmol/l = normal

  • 5.0-6.4 mmol/l = somewhat increased

  • 6.4-7.9 mmol/l = increased

  • >8.0 mmol/l = strongly increased

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Atherosclerosis

  • Gradual narrowing of (coronary) arteries due to build up of plaque

  • Occurs in everyone, but initially remains asymptomatic

  • Obstruction reduces oxygen supply: ischemia

    • If it happens near the heart it is called ischemic heart disease.

    • In the brain it may lead to stroke

    • Outside both of those its peripheral vascular disease

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LDL vs HDL

LDL (consists of 2/3 cholesterol) → Deposits cholesterol in the arteries

HDL (consists of 1/3 cholesterol) → Picks cholesterol up

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LDL evidence for CHD

  • Epidemiological

    • High LDL is correlated with higher CHD risk

  • Genetic

    • People with genetically high LDL levels have higher risk for CHD

  • Pharmacological:

    • Lowering of LDL using drugs reduces CHD risks

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HDL evidence for CHD

  • Epidemiological

    • High HDL is correlated with lower CHD risk

  • Genetic

    • People with genetically high HDL levels do not have a lower risk for CHD

  • Pharmacological

    • Raising HDL using drugs does not reduce CHD risk

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Effect trans fats on blood lipids

  • Trans fat raises blood LDL and lowers HDL when compared with saturated or unsaturated fat

  • Prospective epidemiological studies indicate that trans fat increases CHD risk

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Fat substitution

  • Mouth feel = similar to fat

  • Olestra is an example

    • Sucrose polyester

    • Not absorbed

  • Side effect such as steatorrhea (fat induced diarrhea)

  • Affects absorption of lipid-soluble vitamins

  • Approved for snacks in the US, not approved in the EU

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Constraints of fasting

  • Does not last indefinitely

  • Degradation of protein stores (muscle tissue, other organs) for energy should be avoided

  • Fat largest energy reserve: however, fat can not be converted to glucose

  • The brains is not able to use fatty acids as energy the brain needs glucose

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Energy storage

  • Protein: as structural and functional protein in muscle and other tissue (~15,000 kcal)

  • Carbohydrate: as glycogen in liver and muscle (~2500 kcal in total)

  • Fat: triglycerides in fat tissues (100,000+ kcal)

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Brain metabolism

  • Can not use fatty acids as energy source

    • low levels of B-oxidation

    • Protect brain mitochondria from oxidative stress

  • Glucose primary energy source

  • Accounts for 60% of glucose used by the body

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brain metabolism

  • Can not use fatty acids as energy source

    • Low levels of B-oxidation

    • Protect brain mitochondria from oxidative stress

  • Glucose primary energy source

  • Accounts for 60% of glucose used by the body.

  • Picture shows brain glucose consumption/utilization in the brain during different situations

<ul><li><p>Can not use fatty acids as energy source</p><ul><li><p>Low levels of B-oxidation</p></li><li><p>Protect brain mitochondria from oxidative stress</p></li></ul></li><li><p>Glucose primary energy source</p></li><li><p>Accounts for 60% of glucose used by the body.</p></li><li><p>Picture shows brain glucose consumption/utilization in the brain during different situations</p></li></ul><p></p>
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Early phase of starvation

  • no more glucose enters the bloodstream from diet

  • Consequences: blood glucose levels drop <5mM

  • Need endogenous source of glucose to maintain blood glucose levels

    • Endogenous: growing or originating from within an organism

    • From glycogen stored in liver

    • Glycogenolysis and gluconeogenesis

    • Gluconeogenesis: a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates

    • Glycogenolysis: breakdown of glycogen to glucose.

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Glucose metabolism during starvation

Once no new food enters the body, the body relies on glycogen supplies in the liver to function. This glycogen will run out after a while (one day max) after which gluconeogenesis will take place.

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Early phase of starvation: lipid metabolism

  • Fat breakdown (lipolysis) in adipose tissue becomes activated

  • Consequence: plasma free fatty acid and glycerol levels increase

  • Plasma free fatty acids and glycerol levels continue to rise

  • Fatty acids are taken up by the liver

  • more fatty acids enter the liver than can be fully oxidized

  • Excess fatty acids are converted to ketone bodies or triglycerides

  • Fasting leads to ketogenesis and fatty liver.

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Importance of ketone bodies

  • Body needs an alternative fuel for the brain to replace glucose

  • Ideally, this would be fatty acids as fat is abundant, but these can not be used by brain

  • Instead, the brain can use an intermediate product of fatty acid oxidation: ketone bodies

  • However, ketone bodies can only be synthesized in the liver and this process takes time.

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Use of resources from fed to fasting to starvation

Fed:

  • The body will first use readily available nutrients

Fasting:

  • The body will use glucose from glycogen

  • Then free fatty acids from adipose tissue

  • Then ketone bodies from free fatty acids

Starvation:

  • Glucogenesis

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Distinguish between the different lipoproteins

  • Chylomicrons:

    • Transport dietary triglycerides from the intestine to tissues

    • Lowest density

  • VLDL:

    • Transports triglycerides from the liver to tissues.

    • Low density

  • LDL:

    • Delivers cholesterol to cells

    • Medium density

  • HDL:

    • Removes excess cholesterol from the bloodstream and tissues

    • Highest density

Lowest density = largest molecule