Lipids

What is a fatty acid? Its characteristics?

Hydrocarbon chain with methyl group (non-polar) at one end and carboxylic acid group (polar) at the other end. Insoluble in water.

Classifications of FAs

Chain length, linear vs. branched, even vs. odd number of carbons, saturation, essentiality.

Chain length of FAs

4-24 carbons (most commonly 18 carbons). Mostly even number of carbons due to how fatty acids are synthesized and oxidized.

• SCFAs = 2-5 Cs

• MCFAs = 6-12 Cs

• LCFAs = 13-21 Cs

• VLCFAs = >22 Cs

Odd-chain FAs

Detectable amounts of odd-chain FAs found in meat and dairy products from ruminants and some fatty fish.

• Made by rumen bacteria in ruminants and incorporated into meat and milk fat.

• Fish can make odd-chain FAs in oil-producing glands in addition to eating aquatic organisms that produce them.

• Peroxisomes of human cells can make 17:0 from 18:0 in a process called alpha oxidation that removes a single carbon atom.

Saturation of FAs

The maximum amount of carbons that can be bonded to that hydrocarbon chain is bonded to it.

MUFA and PUFA have double bonds between Cs.

Nutritionally important PUFAs have up to 6 double bonds which are always separated by 3 Cs.

Cis vs trans FAs

This isomerism affects molecular configuration and functionality.

One isomer is when the molecule folds and bends into U-like orientation. Most naturally occurring FAs have this config.

The other isomer is when the isomer extends the molecule into a linear shape like a saturated FA. This naturally occurs in products from ruminants or artificially formed via partial hydrogenation.

Hydrogenation

This is when an unsaturated FA under high H₂ pressure and in the presence of a catalytic metal (nickel, copper alumina, silica, palladium) become saturated fatty acids and have a linear structure despite a double bond.

Why are some fatty acids essential?

Complete exclusion of fat from the diet results in: poor growth/weight loss, dermatitis, and impaired reproduction.

• Females: Irregular menstruation, impaired fetal development, and lactation.

• Males: degeneration of seminiferous tubules

Kidney lesions, early death.

Essential fatty acids

2 unsaturated FAs that cannot be synthesized in the body and must be acquired in the diet: linoleic acid (18:2 n-6 or ∆^9,12), alpha-linolenic acid (18:3 n-3 or ∆^9,12,15).

These are essential because humans do not possess delta-12 and delta-15 desaturases, so we cannot form those double bonds AKA these FAs have double bonds where we cannot add them in the body.

ω-6 fatty acids

Linoleic acid (18:2 n-6 or ∆^9,12): A template to make longer and more unsaturated FAs that are components of cell membranes and precursors of eicosanoids.

Arachidonic acid (20:4 n-6 or ∆^5,8,11,14) Precursor to prostaglandins and leukotrienes. Proinflammatory, platelet aggregation, vasoconstriction. This is conditionally essential if linoleic is not in the diet.

ω-3 FAs

α-linolenid acid: template for other types of omegas. Associated with lower incidence of heart attacks and produces more unsaturated FAs.

EPA: precursor of prostaglandins and leukotrienes with anti-inflammatory, anti-aggregatory, and vasodilatory characteristics.

DHA: Required for brain and eye development in infants, found in oily fish, flaxseed oil, chia seeds, walnuts.

ω-6 and ω-3 fatty acids balance

Our ancestors may have consumed these two essential fatty acids in roughly equal portions.The high intake of omega-6 and low intake of omega-3 in Western diets is predominantly due to processed foods, and vegetable oils and meat instead of fish. There are metabolic consequences of imbalance, and derivatives of these two FAs have critical functions.

Fatty acids in food

In our food, they exist mainly as triglycerides AKA triglycerols.

Triacylglycerols, TAG

Trihydroxyalcohol (glycerol) with 3 fatty acids attached by ester bonds.

They may be simple or mixed and can be all saturated, all monounsaturated, all polyunsaturated or any combination. They exist as fats or oils at room temperature depending on the characteristics of the fatty acids.

Significance of triacylglycerol structure

Our digestion is dictated by where the fatty acids are bound to the glycerol because enzymes are specific for a particular carbon on a glycerol. There is stereospecific numbering; sn-2 hydroxyl group is oriented to the left.

Monoglycerides

Made up of glycerol and one fatty acid. Found in small amounts in olive, grapeseed, and cottonseed oils. Produced industrially by reacting triglycerides with glycerol. Used to improve the texture of foods like margarine, ice ceram, and baked goods.

Diglycerides

Made up of glycerol and two fatty acid chains. Less polar than monoglycerides and have fewer food applications.

Triglycerides

Made up of glycerol and three FA chains. Fats and oils that make up dietary fats. Temporarily convert to monoglycerides and diglycerides during digestion.

Phospholipids

These are phosphate-containing lipids that form the structural basis of cell membranes.

Phospholipid structure

Usually have SFA in position 1 and USFA in position 2 (arachidonic is common). Group in position 3 is bound to phosphate.

Phosphatidylcholine AKA lecithin is most common in mammalian tissues.

Amphipathic molecules: both hydrophilic and hydrophobic.

Sphingolipids

These are found in plasma membrane of all cells and are abundant in the CNS.

Sphingolipid structure

Contain sphingosine (amino alcohol) instead of glycerol. They have a FA attached to the amino (NH) group of sphingosine (R1), a residue attached to the hydroxyl group that defines the type of sphingolipid (R2).

Sterols

These are four-ring steroid nucleus with at least one hydroxyl group. Cholesterol is the most common in humans. Amphipathic, a component of cell membranes, and a precursor for steroids and vitamin D.

Cholesterol ester is the storage and transport form of cholesterol.

Steroids formed from cholesterol

Important precursor for many sterols formed in the body: bile acids; steroid sex hormones like estrogens, androgens, and progesterone; adrenocortical hormones; vit D (cholecalciferol)

Bile

Produced in the liver and helps in fat digestion in the small intestine. Composed of water, bile acids, cholesterol, phospholipids, and other substances. They act to emulsify dietary lipids for digestion and absorption.

Bile acid pool maintenance

Maintained by creation of new from simple precursors (cholesterol) as well as biliary bile acid secretion and intestinal reabsorption. Enterohepatic recirculation of bile acids to the liver to inhibit bile acid synthesis.

What is in bile?

1. Bile acids: cholic acid, deoxycholic acid

2. Bile pigments: bilirubin from hemoglobin breakdown

3. Cholesterol: main excretory route, more adipose tissue → more cholesterol formed → more cholesterol precipitates in gallbladder → can form bile stones

4. Lecithin: somewhat a detergent

5. Mucus

6. Inorganic salts: buffering agents

7. Water

Bile acids are

These are very powerful detergents and good emulsifiers as they have a hydrophilic and hydrophobic end. They can arrange themselves on the surface of small fat particles and break up the fat into small droplets so pancreatic lipase has more surface area to act on.

Enterohepatic circulation

This is the transport of bile acids between the liver and the intestine.

Conjugated bile acids are stored in the gallbladder and released into the intestine after each meal. They are efficiently reabsorbed in the ileum (~95%) and transported back to the liver via hepatic portal circulation.

Phytosterols and stanols

These are contained in plant cell membranes. Stanols are a subcategory of sterols and have one bond less than phytosterols.

Phytosterols structure

Chemical structure: sitosterol 60%, campesterol 35%, and stigmasterol are the most abundant.

Lipids in the GI tract

Lipids don’t like the aqueous environment of the GI tract. TG is the main dietary lipid in a Western diet, which are hydrophobic → emulsification is necessary.

GI lipases (which are esterases) cleave the FA ester bonds within triacylglycerols, phospholipids, cholesterols.

TAG digestion in the mouth and stomach

TAG digestion begins in the mouth and stomach: Lingual lipase comes the serous gland at the base of the tongue. Gastric lipase comes from the chief cells in the stomach.

• These penetrate the milk fat globules and digests fat in the stomach (10-30% of total fat digestion, and is important for fat digestion in a suckling infant)

• Secretion is stimulated by high dietary fat and swallowing.

• Mainly digest short and medium chain FAs at sn-3 position

Emulsification of lipids

These are muscle contractions and movement of fat through the pyloric sphincter breaking large fat globules into tiny fat droplets. As we break down triglycerides, we form di- and monoglycerides that become more polar. Bile acids are

CCK and secretin

Lipid digestion in the intestine

Emulsification continues with mechanical shearing.

Digestion and absorption of lipids requires

• Lower acidity

• Appropriate lipases

  • Colipase

  • Bile salts

  • Calcium

The small intestine is very efficient in digesting large quantities of TAG and small fat droplets get smaller resulting in micelles containing MAG and FFAs.

What is the usual product of digestion in the mouth and stomach of fats?

Diacylglycerol. Because

What is the usual product of digestion in small intestine of fats?

Monoacylglycerol. Because

Phospholipid digestion

Hydrolyzed by phospholipase A₂, which is made and secreted by the pancreas. Bile releases phospholipids (phosphatidylcholine) into small intestine, ~5x more than in diet. Both dietary and biliary PL are hydrolyzed by phospholipase A₂. Most of what we digest of phospholipids comes from bile not diet.

End product of PL digestion is lysoPL +FFA.

Cholesterol ester digestion

Cholesterol esterase cleaves the FA off the cholesterol ester and end up with cholesterol and a FFA. Phytosterol esters are also digested in this way.

Esterification

When we reform ester bonds between FAs or whatever molecule we just broke it off of.

Absorption of lipids

MAG, FFA, and lysoPL need to be absorbed. Diffusion across the brush border happens when the conc in he intestsinal lumen exceeds that of the cell.

The mechanism for moving across the brush border membrane is not fully understood, but we have ideas:

• Protein-independent diffusion model

• Protein-depen

Branched-chain FAs

These are saturated FAs with one or more methyl groups attached along the hydrocarbon chain. Most of these are 14-16 C chain with a methyl group on ω-2 or ω-3 and mainly in meat/dairy products and fatty fish.

Biological role of phospholipids

Role is to attract water molecules, contribute to cell membrane structure and fluidity, cell signaling (insulin signaling), cell functions such as anchoring proteins, blood clotting, inflammation, growth and differentiation, etc.

Sphingolipid types

• Ceramide: no attachment on R²

• Sphingomyelin: phosphocholine on R² of ceramide

• Cerebrosides: galactose or glucose on R² that acts as insulators in nerve impulse conduction.

• Gangliosides: Oligosaccharide on R² that acts as cellular recognition markers and receptors for some hormones and toxins.

What makes a bile salt different from bile acid?

Bile salts have a glycine attached to it, while bile acids do not.

Why are phytosterols important?

They can produce reductions in blood cholesterol because of their similarity to cholesterol, so they displace cholesterol and reduce its absorption. Good sources are seed oils, legumes, nuts, and seeds.

Recommended intakes of FAs

Unsaturated FAs should be the primary source of dietary fat.

• Flax seed oil has the highest % of alpha-linolenic FAs, then canola and soybean oils.

• Consumption of EPA and DHA from fatty fish can avert deficiencies of alpha-linolenic.

Limit SFA intake to <10% total caloric intake.

Minimize trans FA intake.

Cholesterol absorption

We absorb this into our body from the diet and bile. What is not absorbed is excreted in the feces. Cholesterol is present in the micelles for delivery to enterocyte. Uptake is mediated by the Niemann-pick C1 Like protein (NPC1L1).

Sterol carrier proteins bind cholesterol in the cytosol and it may incorporate itself into the enterocyte membrane. Most cholesterol is esterified for transport out of the cell by chylomicrons (cholesterol acyltransferase 2 (ACAT2) esterifies cholesterol)

Phytosterol absorption

Also transported into intestinal cell by NPC1L1. Two proteins—ABCG5 and ABCG8—located next to NPC1L1 in the brush border membrane immediately redirect phytosterols back out to the intestine, in this process they also redirect some cholesterol back so reduces blood cholesterol by >10%.

How are lipids packed to be released into the circulation?

Lipids are re-esterified in the Er and aggregate into large lipid-protein structures called chylomicrons, which occurs so they can be transported in the aqueous bloodstream. They are packaged in the enterocyte, and then go into the lymph, and then go into the blood.

Chylomicrons and their transport

Fully formed chylomicrons are released via exocytosis at the basolateral side of the enterocyte and the enter the lacteals of the lymphatic system.

Medium-chain FA release into circulation

Metabolism in the mucosal cell

Lipoproteins

These transport cholesterol, triglycerides, and other fat-soluble compounds in the bloodstream. They are complex particles composed of lipids and proteins. Apolipoproteins are on the surface.

Lipoprotein structure

Monolayer phospholipid membrane of mainly polar membranes and free cholesterol so that hydrophobic, nonpolar lipids are in the center. Apolipoproteins AKA apoproteins are on the surface to create structural stability and serve as enzyme activators or ligands for cell receptors.

Lipoprotein classes

LDL: made up mainly of cholesterol, so it brings cholesterol to parts of our bodies.

HDL: made mainly of

IDL:

VLDL:

Chylomicrons:

Lipid transport systems

Exogenous, endogenous, reverse

Exogenous lipid transport system

Transports TAG from the intestine to peripheral tissues for utilization or storage. Chylomicrons deliver remaining cholesterol to the liver after all dietary TAG are delivered.

Endogenous lipid transport system

Involves VLDL, IDL, and LDL. Transports TAG and cholesterol from liver to peripheral tissues for utilization or storage. Lipids come from an internal source—the liver.

Reverse cholesterol transport

HDL picks up excess cholesterol from peripheral tissues and delivers it to the liver for excretion from the body or conversion to other important molecules. HDL also transports cholesterol to adrenal gland, ovaries, and testes.

Chylomicron synthesis + entering blood process

After a meal with fat, exogenous lipids are packed into CMs within the enterocyte and distributed to extrahepatic tissues—muscle and adipose tissue. Contain mostly TAG and apoA1 and apoB48. CM acquires more apoproteins from HDL as the lipoproteins interact in the circulation and then enable the metabolism, distribution, and disposal of dietary TAG.

CM enter the blood for up to 14 hrs after a fat-rich meal. Blood TAG concentration usually peaks 30 min - 3 hrs after a meal and returns to near normal within 5-6 hrs.

The presence of TAG-rich CM accounts for the turbidity of postprandial plasma and can interfere with clinical readings for “fasting triglyceride” values, so true readings usually 12 hrs of fasting.

Where/how are chylomicrons dropping off TAGs?

They interact with different tissues (skeletal muscle, heart muscle, and adipose tissue, but not the liver) with the enzyme lipoprotein lipase. Enzyme apoC-2 activates the LPL. CM dock on the cell surface, LPL hydrolyzes the TAG into 3 FFA + glycerol that are quickly taken into the cell. As TAG leaves, the CM shrinks and becomes a chylomicron remnant and can be sent back to the liver.

What happens to the chylomicron remnant?

These particles separate from LPL and reenter circulation. May donate some of its apoproteins to HDL. The chylomicron remnants are taken up by hepatocytes via the LDL receptor-related protein 1 that recognizes apoE. It is absorbed into the hepatocyte and hepatic lipase hydrolyzes remaining TAG and PL of CM and then the liver will decide what to do.

Metabolism in adipocytes in FED state

• LPL hydrolyzes TAG in CM causing FFA and MAG to enter the adipocyte.

• Metabolic pathways favor energy storage as TAG in this state

• Insulin stimulates LPL, increasing the uptake of FFA and MAG in adipocytes. Lipogenesis is stimulated by insulin by promoting the entry of glucose into the cell for lipogenesis so it can create its own glycerol to package up FFA as triacylglycerol.

Glucose → Acetyl-Coa → acyl-CoA → fatty acids (lipogenesis)

Glycolysis in adipocytes → glycerol-3-P, which is used for TAG synthesis

Metabolism in hepatocytes in the FED state

1. Dietary nutrients (FFAs, chylomicron remnants, etc.) enter liver via hepatic portal vein. Glucose converted to glycogen or enter glycolysis.

2. AAs enter the AA pool; some are metabolized to pyruvate and oxaloacetate

3. Serum FFA, bound to albumin, enter the FA pool, converted to TAG

4. CR enter the hepatocyte by endocytosis and are taken up by a lysosome; FFA, MAG, and cholesterol are released

5. TAG, Chol, and PL are packaged with apoproteins, enter circulation as VLDL

6. VLDL deliver TAG to muscle and adipose tissue

VLDL

These transport excess lipids out of the liver. The TGs come from chylomicron remnants, excess monosaccharides and AAs,

Endogenous lipid transport system

VLDL → IDL → LDL (the most atherogenic)

1. Nascent VLDL made in Golgi apparatus of liver

2. Additional apoproteins C and E are transferred from HDL

3. FAs from TAG are hydrolyzed by lipoprotein lipase found mainly in muscle and adipose tissue

4. As the TAG is removed from he VLDL, the particle becomes smaller and becomes an IDL.

   1. Further loss of

Influences on LDL uptake

LDL receptors

Cholesterol synthesis and storage

Endogenous lipid transport

What and why reverse cholesterol transport?

Every cell in the body can synthesize cholesterol. However, mammals lack the oxidative enzymes for cholesterol degradation therefore transport of cholesterol from peripheral cells to the liver for excretion is critical for maintaining cholesterol homeostasis. HDL in blood picks up excess cholesterol from peripheral tissues and delivers it to the liver for excretion via bile. The amount of cholesterol used to produce other compounds is very small compared to amount excreted through bile, so the role of HDL is very important.

Reverse cholesterol transport process

1. Liver and intestine secret apoA-1, HDL’s main protein. Also can be from CM and VLDL during TAG hydrolysis.

2. ApoA-1 acquires PL and Chol from interactions with liver ABCA1 receptor, resulting in nascent discoidal HDL.

3. Nascent HDL picks up more PL and Chol via ABCA1, and additional Chol via Sr-B1 in peripheral tissues.

4. LCAT on HDL esterifies Chol to CE, migrates to the particle core

Postabsorptive state lipid metabolism

When there is increased energy needs, there is lipolysis. Hydrolysis of TAG releases FFA to blood, only adipocytes do this. FFA-albumin travel to energy-requiring cells. FAs are catabolized through mitochondrial beta-oxidation of FAs. Ketones are formed when insufficient dietary energy is available to send to the brain and RBC.

Integrated lipid metabolism

Uptake and release of FA from adipose tissue throughout the day meets energy needs in the face of sporadic energy consumption.

Synthesis of lipids in the FED state

S

Synthesis of fatty acids

This takes place in the liver, lungs, adipocytes, lactating mammary glands, brain, kidneys, and sometimes muscles.

Occurs in cytosol, with the sequential assembly of “starter” acetyl-CoA with units of malonyl-CoA. Elongation of FA chain by adding acetyl-CoA molecules

First we need to move acetyl-CoA form the mitochondrion to the cytosol, so it must be converted to citrate first.

Acetyl-CoA carboxylase synthesizes malonyl-CoA from acetyl-CoA. This is a regulatory step and the enzymes involved in this process is a called the fatty acid synthase system.

The starter molecules attach to complex carrier proteins and enzymes: acyl carrier protein (ACP) and the condensing enzyme (CE). We take the acetyl group and continually add it to a 2-carbon unit. The energy that we use is NADPH because it is donating its H group, we store high energy H’s in fats.

Elongation of the FA chain

Chain is started with 2-carbon acetyl-CoA and then malonyl-CoA

Eicosanoids

Physiological effects of n-6 vs. n-3 derived messengers

Synthesis of TAG and PL

Lipid catabolism in the POSTABSORPTIVE state

Mobilization of adipose TAG

Catabolism of FAs

Oxidation of FAs occurs in the mitochondria and produces energy via oxidative phosphorylation.

1. Activation of FA with CoA:

1. Transport of FA from cytoplasm into mitochondria via carnitine

2. Beta-oxidation in the mitochondria

Beta-oxidation of SFAs

Beta-oxidation of UFAs

For (n-9) oleic acid, this process sequentially removes three acetyl-CoA producing a shorter FA with the double bond between delta-3 and delta-4

Beta-oxidation of odd-chain FAs

This leaves us with an odd number at the end. Process occurs normally, with the final products being acetyl-CoA and the three carbon propionyl-CoA.

Oxidation of propionyl-CoA requires additional enzymes that use biotin and B12 as coenzymes, producing succinyl-CoA, which can enter the TCA cycle.

Can also be converted to glucose, making odd-chain fatty acids uniquely glucogenic (a precursor for gluconeogenesis) among FAs.

Energy from FA oxidation

Beta-oxidation of one molecule of palmitic acid requires 7 passages through the pathway, and produces 8 acetyl-CoA, 7 FADH₂, and 7NADH.

These FADH₂ and NADH can then directly enter into the ETC and yield an average of

The acetyl-CoA’s are completely oxidized to CO₂ and H₂O by the TCA cycle and oxidative phosphorylation, with an average yield of 12(10) ATP/mole.

In the palmitic acid example, we can yield a net of 129 ATP.

Ketones are…

These are made from excess FFA. Accelerated FA oxidation means that more FFA released from adipocytes than tissues can oxidize.

However, the RBCs and brain cannot use FA for energy. Excess FA enter the liver → beta-oxidation → acetyl-CoA → ketones. Synthesized only in liver mitochondria. Saves glucose for the cells that must use it. Ketones leave the liver and travel to the brain and muscle as the liver does not use ketones.

Ketogenesis

Liver converts excess FFA to ketone bodies: acetone, acetoacetate, and beta-hydroxybutyrate. This is a mitochondrial process in low carbohydrate or hypocaloric diets. KB used by some brain cells via ketone → acetyl-CoA → TCA cycle.

Ketosis vs ketoacidosis

A mild increase in ketone bodies (as in body fat loss and keto diets) to 0.5-3 mmol/L or 9mg/dL.

vs.

Dangerously high levels of ketone bodies in the blood (as in uncontrolled DM, very low CHO diets for long time, or starvation).

Why do ketone bodies accumulate in the blood?

If there are more of these in the blood than the tissues can utilize, the tissues will not take these in and then send them into the TCA cycle as we also lack the intermediates to push the process along, which requires some carbohydrates because we need adequate supply of 4-C molecules (formed mainly from pyruvate), so inadequate CHO means inadequate pyruvate and slow TCA cycle and low pool of oxaloacetate to combine with acetyl-CoA for TCA cycle. This leads to acetyl-CoA accumulation and increased KB formation.

Untreated ketoacidosis can lead to low blood pressure, dehydration, coma, and death :o

Lipid metabolism regulation

Hormonal regulation:

• Insulin increases FA synthesis, TAG storage, and decreases lipolysis. Glucose → acetyl-CoA → FA → TAG storage.

• Glucagon and epinephrine: increases lipolysis, FA oxidation, decreases lipogenesis. Adipose TAG → FAs → beta-oxidation → ATP/ketones

Enzyme regulation: certain enzymes can be activated by insulin or glucagon and that can either spur a pathway forward or slow it down.

• Acetyl-CoA will

• Hormone-sensitive lipase (HSL):

• Carnitine transport: inhibited by malonyl-CoA → prevents FA oxidation during synthesis.

Atherosclerosis development and lipids

A degenerative disease of the vascular endothelium. Slow, asymptomatic build up or plaque (lipids, cholesterol, and calcium) within artery walls, causing them to narrow and harden, which restricts blood flow. Considered a disease of dyslipidemia and immune system-induced inflammation.

This atherogenic process involves some immune system cells that cause a pro-inflammatory environment, and lipids—primarily cholesterol and cholesterol esters.

Begins when LDL and IDL infiltrate artery walls and are oxidized, triggering an inflammatory response because your body recognizes that they should not belong there. This leads to the formation of foam cells and fatty lesions. The macrophages try to deal with the LDL and IDL in your artery walls, and when they are overwhelmed, there is a continued inflammatory signaling → greater immune response → creates a barrier between prothrombotic factors in the lesion and procoagulant factors in the blood → plaque formation.

Plaque formation in atherosclerosis

This creates a partial occlusion of the artery lumen, which can cause symptoms of chest pain or leg pain during exertion.

Continued inflammation within plaque, which makes them unstable and prone to rupture, and promotes thrombus formation and possible ischemic events (myocardial infarction or stroke).

Plaques and clots

A thrombus can form if a part of the cap over the plaque opens. If the thrombus breaks off, it becomes an embolus and travel and block a vessel downstream which leads to blood clots or strokes.

The lipid hypothesis (relationship between lipids in blood and plaques in ASCVD)

TAG, LDL- and HDL-Chol. Uns

Particle size matters: LDL particles are more atherosclerotic as they are smaller and denser and are more likely to penetrate the artery wall and become oxidized and initiate plaque formation.

Dietary vs. plasma cholesterol

We believed that there was a link between ______ and _____ cholesterol but this has been contested. This dietary restriction is no longer recommended.

Individuals with hyperlipidemia have higher risk of ASCVD. High HDL + low LDL = healthy! Ratios of ApoA (HDL) to Apo B (LDL) are used to assess CVD risk: risk decreases as ratio decreases.

FA saturation and CVD

Unsaturated FAs decrease risk of CVD. Effects of dietary FAs are due to changes in membrane lipid composition, cellular metabolism, intracellular signal transduction, and the regulation of gene expression. It is recommended to reduce SFA intake with PUFA (decrease LDL-C) and MUFA (total C and LDL-C).