Lipids: Foundational Knowledge

What is cholesterol?

A type of lipid called a sterol.

How does cholesterol help the cell membrane?

Helps maintain membrane structure and fluidity

How is cholesterol used in steroid hormones?

To produce hormones such as cortisol, aldosterone, estrogen, and testosterone

How is cholesterol involved in Vitamin D synthesis?

Serves as a precusor

How is cholesterol used in bile acids?

To produce bile acids that help digest and absorb dietary fatsd t

Cholesterol isn’t always bad. How does it turn bad?

When excessive amounts of cholesterol are carried in certain lipoproteins like LDL.

What are triglycerides?

The body’s primary form of stored fat.

What makes up a triglyceride?

One glycerol molecule attached to 3 fatty acids

What is triglycerides main purpose?

Provide and store energy

How are cholesterol and triglycerides similar and how are they different?

The are both lipids that perform different functions.

Why do we need lipoproteins?

Lipids are not water soluble. Blood is mainly water so lipids don’t dissolve well in it resulting in them not being able to travel through the blood on their own. Lipoproteins help the lipids travel through the blood.

How do lipoproteins help the lipids travel through the blood?

They have an outer surface that interacts with water and an inner core containing cholesterol esters and triglycerides.

List the 5 major lipoproteins.

Chylomicrons, VLDL, IDL, LDL, HDL

What do chylomicrons do?

Transport dietary triglycerides and cholesterol from the intestines to tissues and eventually the liver

What is VLDL (Very-low-density lipoprotein)?

Its produced by the liver to transport triglycerides to tissues

What is IDL (intermediate-density lipoprotein)?

Formed when VLDL loses triglycerides. It can be taken up by the liver or futher converted into LDL

What does LDL (low-density lipoprotein) do?

Delivers cholesterol through the bloodstream to tissues that need it

What does HDL (high-density lipoprotein) do?

Helps remove excess cholesterol from peripheral tissues and transport it toward the liver through reverse cholesterol transport

What is the main treatment target in dyslipidemia?

Lowering LDL cholesterol

What are the 2 lipid pathways?

Dietary and Liver-produced

What makes up the Dietary lipid pathway?

Intestines —> Chylomicrons —> deliver triglycerides to tissues —> remnants return to liver

What makes up the Liver-produced lipid pathway?

Liver produces VLDL —> IDL —> LDL —> delivers cholesterol to tissues

Describe the different pathway HDL goes through.

It uses reverse cholesterol transport, which helps move excess cholesterol away from tissues toward the liver.

What makes LDL bad?

When too many LDL particles circulate, some can become trapped in arterial walls. This contributes to inflammation and atherosclerotic plaque formation.

What makes HDL good?

It removes cholesterol from tissues.

Does simply increasing the HDL-C number with medication prevent cardiovascular disease?

No, that’s why we primarily lower LDL-C because they are the main cause of ASCVD

What is dyslipidemia?

A disorder characterized by abnormal levels of lipids or lipoproteins in the bloodstream

Does dyslipidemia always mean high cholesterol?

No

List the reasons a patient can have dyslipidemia.

Elevated LDL cholesterol, Elevated triglycerides, Decreased HDL cholesterol, A combination of lipid abnormalities

Dyslipidemia is clinically important. Why?

Cholesterol and Triglycerides serve essential functions in the body. When their concentrations become abnormal, particularly elevated LDL-C, increase the risk of atherosclerosis.

What is atherosclerosis?

The accumulation of cholesterol-rich plaque within arterial walls

What can artherosclerosois lead to?

Coronary artery disease, Myocardial infarction, Ischemic stroke, Peripheral artery disease

What does it mean by dyslipidemia being a modifiable cardiovascular risk factor?

It means it is treatable which works to reduce a patient’s risk of developing cardiovascular complications

What should you be able to explain regarding dyslipidemia?

That it is an abnormality in lipid or lipoprotein levels, including elevated LDL-C, elevated triglycerides, decreased HDL-C, or combinations of these abnormalities.

What is the name for elevated LDL-C?

Hypercholesterolemia

LDL is a major _______ lipoprotein.

Atherogenic

Define atherogenic.

Something capable of promoting atherosclerotic plaque formation

What is the name for elevated triglycerides?

Hypertriglyceridemia

Triglycerides are mainly transported by ___________?

chylomicrons and VLDL

List some common factors that cause elevated triglycerides.

Obesity and insulin resistance, Poorly controlled diabetes, excessive alcohol intake, diets high in refined carbohhydrates, certain medications and genetic disorders

Why are elevated triglycerides concerning?

Increases cardiovascular risk and acute pancreatitis

What are the triglyceride thresholds?

Normal <150 mg/dL

Borderline high 150-199 mg/dL

High 200-499 mg/dL

Very High >_ 500 mg/dL

What are the common low HDL-C thresholds?

Men <40 mg/dL Women <50 mg/dL

Define total cholesterol.

Measures cholesterol carried by the major circulating lipoproteins

What are the total cholesterol thresholds?

Desirable <200 mg/dL Borderline high 200-239 mg/dL High >_ 240 mg/dL

Define mixed dyslipidemia.

A patient who has more than one lipid abnormality

How does primary dyslipidemia occur?

Due to inherited genetic abnormalitites that affect how the body produces, transports, or clears lipids and lipoproteins

Can a patient have abnormal cholesterol levels even with a healthy diet and lifestyle? explain.

Yes because their body may not regulate lipids normally

What 2 pathways does the body use to obtain cholesterol and triglycerides?

Exogenous and Endogenous pathways

Define the Exogenous pathway.

Lipids that come from your diet and are absorbed by the intestines

Define Endogenous pathway.

Lipids produced or packaged by your liver

Say you eat food. After the triglycerides and cholesterol enter the small intestine what happens next?

Chylomicrons package the absorbed lipids for transport

Once the chylomicrons package the absorbed lipids for transport what then happens?

Lipoprotein lipase (LPL) removes the triglycerides and releases fatty acids to tissues

After the lipoprotein lipase removes the triglycerides and releases fatty acids to tissues, what happens?

chylomicron remnants carry the remaining lipids back to the liver

After chylomicron remnants carry the remaining lipids back to the liver what happens?

ApoE helps the remnant get taken up by the liver.

What exactly does LPL do?

It breaks down triglycerides inside circulating lipoproteins into fatty acids, which are then used by the muscles for energy and stored in adipose tissue for future energy

List all of the apolipoproteins.

ApoB-48

ApoC-II

ApoC-III

ApoE

Define ApoB-48.

Structural protein of chylomicrons

Define ApoC-II.

Activates LPL so triglycerides can be broken down

Define ApoC-III.

Inhibits LPL activity

Define ApoE.

Helps the liver recognize and clear chylomicron remnants

Define the Endogenous pathway.

The process by which the liver produces and transports lipids throughout the body using lipoprotein VLDL

In the endogenous pathway the liver releases VLDL which carries primarily triglycerides into the blood, what happens next?

LPL removes the triglycerides making VLDL smaller turning into IDL

The IDL can return to the liver or undergo futher metabolism, then what happens?

LDL is formed which delivers cholesterol to tissues

Why does VLDL eventually become LDL?

As triglycerides are removed, the particle becomes smaller and relatively richer in cholesterol. That is why the endogenous pathway follows: VLDL —> IDL —> LDL

Why doesn’t all IDL turn into LDL?

because some is removed by the liver

When LDL circulates through the bloodstream carrying cholesterol, what do liver cells have and what do those things do?

They have LDL receptors which recognize ApoB-100 on LDL particles

What happens when the LDL binds to the LDL receptors? Why does this matter?

The particle can be taken into the cell and removed from circulation. If LDL clearance is impaired, LDL remains in the bloodstream longer, contributing to elevated LDL-C and increased ASCVD risk

What pathway does the liver use to make cholesterol from smaller molecules?

Acetyl-CoA —> HMG-CoA —> Mevalonate —> Cholesterol

In the liver cholesterol synthesis pathway, what enzyme catalyzes the conversion of HMG-CoA to mevalonate? What is this step called?

HMG-CoA reductase; the rate-limiting step

The HMG-CoA enzyme is important. Why?

Because statins inhibit HMG-CoA reductase

What happens when a statin inhibits HMG-CoA?

Hepatic cholesterol synthesis ↓

Liver cells respond by ↑ LDL receptors

More LDL is removed from the blood

Circulating LDL-C ↓

HDL becomes important when tissues have excess cholesterol. Why?

Because HDL uses the reverse cholesterol transport, which moves cholesterol from peripheral tissues back toward the liver

Which apliopoprotein does HDL use in the reverse cholesterol transport?

ApoA-I

Sumarize the difference between LDL and HDL. What do each one do in simple terms?

LDL helps deliver cholesterol, HDL helps collect excess cholesterol for transport toward the liver