Season 1 Episode 5: Lipoproteins

Picture an atherosclerotic artery as a crime scene. Cholesterol piles up on the walls — thick deposits blocking what should be a free-flowing highway of blood. For decades, cholesterol was blamed as the culprit. But here’s the twist: cholesterol is just the passenger. The real suspects are the lipoproteins — the vehicles smuggling cholesterol into places it doesn’t belong. 

In this episode of LipidCurious, we’re stepping into the role of detective. We’ll assemble a lipoprotein from scratch, meet the different lipoproteins, and follow their pathways through the body. 

Here’s what we’ll cover together:

1.    Structure and types of Lipoproteins

2.    Exogenous and endogenous pathways of lipid metabolism

3.    How cholesterol-lowering medications leverage lipid biology

Bonus: The Visual Guide for this episode is waiting for you — click here. For the full collection of visuals across episodes, visit the Podcast page.

Download the Free LipidCurious Starter Kit here

Questions or feedback? Reach out at hello@lipidcurious.com

Disclaimer: This podcast is for educational purposes only. It is NOT medical advice.

Transcript

SEASON 1, EPISODE 5: LIPOPROTEINS

Picture an atherosclerotic artery as a crime scene. Cholesterol piles up on the walls — thick deposits blocking what should be a free-flowing highway of blood. For decades, cholesterol was blamed as the culprit. 

But here’s the twist: cholesterol is just the passenger. The real suspects are the lipoproteins — the vehicles smuggling cholesterol into places it doesn’t belong. Every atherosclerotic plaque begins with one of these lipoprotein particles breaking in, unloading its cargo, and disappearing — leaving cholesterol behind at the scene. 

So today, we’re stepping into the role of detective. We’ll assemble a lipoprotein from scratch, meet the different lipoproteins, and follow their pathways through the body. 

And if you’re tempted to tune out because this sounds too basic, stick with me —mastery of these foundations is what lets you apply the right medication to the right patient.

Welcome to LipidCurious — the podcast dedicated to demystifying lipids for medical boards and real-world clinical practice.
I’m your host, Dr. Vishnu Priya Pulipati — a board-certified Endocrinologist and Lipidologist.

This is Season 1, Episode 5 — Lipoproteins.

Here’s what we’ll cover together:

1.    Structure and types of Lipoproteins

2.    Exogenous and endogenous pathways of lipid metabolism

3.    How cholesterol-lowering medications leverage lipid biology

This episode comes with a bonus visual handout in the show notes. And if you’re the kind of person who wants everything in one place, head to lipidcurious.com — you’ll find the complete set of visuals from season 1 plus a free Starter Kit packed with practical clinical guides, cheat sheets, and quick references you can actually use in your practice.

And as always, a reminder — this podcast is for education only, not medical advice.

Alright, let’s get into it.

Now let’s assemble a Lipoprotein:

I like to think of lipoproteins as floating shuttles engineered to carry lipid cargo safely through the watery bloodstream. Lipoproteins can take different shapes. For simplicity, let’s picture them as spherical tennis balls floating in the bloodstream. 

Step 1 — The shell: A single layer of phospholipids and free cholesterol. Think of it like a waterproof lining around the cargo.

Step 2 – The Cargo: Inside, we pack the VIPs: triglycerides and cholesteryl esters.

Step 3 – The Apolipoproteins: Think of apolipoproteins as the barcodes and ID tags. They tell each particle where to go: ‘Deliver here, pick up there.’ Example ApoB it is a big molecule that wraps around the lipoprotein particle like a belt, this carries the barcode the liver recognizes and pulls LDL into it. We’ll dive deeper into this in a future episode.

So a lipoprotein isn’t just a blob of fat. It’s a sophisticated shuttle system.

Types of Lipoproteins

Lipoproteins can be divided into seven classes based on size, lipid cargo, and their apolipoproteins 

1.    Chylomicrons are large, triglyceride-rich particles made by the intestine. They transport dietary fat to peripheral tissues and the liver. Because of their large size, they usually don’t enter the arterial wall to cause atherosclerosis — but in excess they can trigger pancreatitis.

2.    Chylomicron remnants: smaller, cholesterol-rich particles left after chylomicrons deliver their triglycerides. Pro-Atherogenic. 

3.    Very Low Density Lipoprotein (VLDL): triglyceride-rich particles made by the liver. 

4.    Intermediate Density Lipoprotein (IDL): As triglycerides are stripped away, they progressively shrink and become cholesterol-dense IDL 

5.    Low Density Lipoprotein (LDL) is the main cholesterol carrier and most atherogenic.

6.    HDL — the garbage trucks that collect cholesterol and bring it back to the liver.

7.    Lp(a) — a special LDL particle with an extra protein Apo(a) that makes it both atherogenic and thrombogenic. We’ll give it its own episode.

Journey of Lipoproteins

The journey of lipoproteins is like a choreographed dance. I’ll walk you through the main moves here; the detailed enzymes and transporters are in the visual guide at lipidcurious.com.

EXOGENOUS PATHWAY:

After a fatty meal, digestion begins in the stomach with lingual and gastric lipases starting to break down triglycerides.

In the duodenum, gall baldder squeezes out bile salts — emulsifying big fat globules into tiny droplets, increasing the surface area.

Then in the jejunum, pancreatic lipase chops triglycerides into fatty acids and glycerol. Cholesterol on the other hand, while partially present in food, most of it is recycled bile. 

These digested lipid products hitch a ride in micelles — tiny ferries that carry fatty acids, cholesterol, and fat-soluble vitamins to the intestinal lining. 

Once inside the intestinal cell, fatty acids and glycerol are reassembled into triglycerides, cholesterol is esterified, and everything is packaged with ApoB-48 into large particles called chylomicrons.

Chylomicrons leave through the lymphatics and enter the bloodstream. There, they borrow ApoC and ApoE from HDL and meet lipoprotein lipase (LPL), which clips triglycerides into free fatty acids for muscle and fat to use.

As triglycerides are stripped away, chylomicrons shrink into remnants — richer in cholesterol. ApoE then guides these remnants back to the liver for clearance.

So in short: Food → emulsification → pancreatic lipase digestion → intestinal absorption → chylomicron formation → LPL unloads triglycerides → chylomicron remnant → cleared by the liver.

ENDOGENOUS PATHWAY

Now let’s switch to the endogenous pathway — the liver’s way of packaging and shipping fats.

Inside the liver, triglycerides and cholesterol esters are loaded with ApoB-100 called VLDL. The more triglycerides the liver has, the more VLDL it produces — and conditions like diabetes mellitus, obesity, and metabolic syndrome can really turn up that production.

VLDL enters the bloodstream, where lipoprotein lipase (LPL) trims off triglycerides, releasing fatty acids for muscle and fat. As this happens, VLDL shrinks into IDL, which is richer in cholesterol. Some IDL particles head back to the liver, while others are trimmed further by hepatic lipase until they become LDL.

LDL is mostly cholesterol esters wrapped in ApoB-100. Most LDL is cleared by LDL receptors in the liver, with the rest taken up by other tissues. How much LDL you see in the blood depends on two things: how much is made and how efficiently it’s cleared — both tightly linked to the number of LDL receptors available.

Here’s the key clinical point: when the liver’s cholesterol runs low, it makes more LDL receptors, which pull more LDL out of circulation. Another key player here is PCSK9, a protein that controls how many LDL receptors survive on the liver surface. The more active PCSK9 is, the fewer receptors survive, and the higher LDL cholesterol climbs. 

How cholesterol-lowering medications leverage lipid biology

Most of our current cholesterol-lowering therapies capitalize on the knowledge of lipid biology and work by either lowering the liver’s cholesterol supply or preserving LDL receptors so more LDL can be cleared.

Bile acid sequestrants bind bile acids in the gut and stop them from being reabsorbed. The liver has to make new bile acids, using up its cholesterol and forcing it to increase LDL receptors.

Ezetimibe blocks the NPC1L1 transporter in the intestine, so less cholesterol is absorbed from the diet and bile.

Statins block HMG-CoA reductase, the key enzyme in cholesterol synthesis. Bempedoic acid works a step earlier, at ATP-citrate lyase. Both reduce the liver’s cholesterol pool, which drives up LDL receptor numbers.

PCSK9 inhibitors prevent PCSK9 from destroying LDL receptors. More receptors survive on the liver surface, and more LDL is cleared from circulation.

Fibrates and omega-3 fatty acids mainly target VLDL, reducing triglyceride-rich precursors of LDL.

So here’s the takeaway for this episode: 

1. Retention of excess Lipoproteins within the arterial wall is the real culprit driving atherosclerosis.

2. Lipoproteins are like shuttles — their structure, cargo, and apolipoproteins determine where cholesterol ends up.

3.    Targeting lipoprotein pathways helps turn complex biology into effective treatments for dyslipidemia. 

Join me in two weeks for our next episode — we’ll unpack HDL and explore how reverse cholesterol transport helps clear cholesterol from the body. 

Thanks for tuning in to LipidCurious. If today’s episode was helpful, share it with a colleague — let’s grow this community of lipid-curious clinicians. I’d love to hear your suggestions, feedback, or if you want to say hi to me, you can always reach me at hello@lipidcurious.com. Be sure to subscribe or follow, so you don’t miss what’s next. And don’t forget — you can download the free Starter Kit and season 1 visual guide at www.lipidcurious.com

Until next time — stay curious, and stay confident.
Signing off, Dr. Pulipati.

Bonus: The Visual Guide for this episode is waiting for you — click here. For the full collection of visuals across episodes, visit the Podcast page.

Download the Free LipidCurious Starter Kit here

Questions or feedback? Reach out at hello@lipidcurious.com