17 - Clinical Aspects of Energy and Metabolism 3

What does a fasting plasma lipid profile represent, and which lipoproteins are present?

A fasting plasma lipid profile reflects the levels of triglycerides and cholesterol in circulation after chylomicrons have been cleared (typically 8–12 hours post-meal). In this state, the profile includes:

• VLDL: carries endogenous triglycerides

• IDL and LDL: carry cholesterol (especially LDL, the major carrier of plasma cholesterol)

• HDL: involved in reverse cholesterol transport

What is the Friedewald formula for calculating LDL cholesterol, and when is it invalid?

LDL-C = Total Cholesterol – HDL-C – (Triglycerides ÷ 5)
(All values in mg/dL)

• The formula uses triglycerides ÷ 5 to estimate VLDL cholesterol because VLDL particles are typically composed of about five times more triglyceride than cholesterol.

• The formula becomes inaccurate when triglycerides > 400 mg/dL, as VLDL composition varies and may include chylomicrons.

What is dyslipidemia, and what are its main causes?

Dyslipidemia refers to abnormal levels of lipids or lipoproteins in the blood. It includes:

• Hyperlipoproteinemia: Elevated levels of cholesterol and/or triglycerides (e.g., high LDL, VLDL, or chylomicrons)

• Hypolipoproteinemia: Abnormally low levels of lipoproteins

What LDL-C level is considered abnormal or high?

LDL-C ≥ 130 mg/dL is generally considered elevated, with ≥ 190 mg/dL classified as very high and typically prompting evaluation for familial hypercholesterolemia.

Why can high LDL-C result from both LDL receptor defects and ApoB-100 abnormalities?

• LDL receptor (LDLR) dysfunction – most common cause, as in familial hypercholesterolemia, where LDL cannot be effectively taken up by cells.

• ApoB-100 abnormalities – since ApoB-100 is the ligand that binds LDL to its receptor, a defect in ApoB impairs LDL receptor binding even if the receptor is normal.

Both lead to reduced LDL clearance and increased plasma LDL-C.

Why does a plasma sample appear murky or turbid in cases of high chylomicrons or VLDL?

Chylomicrons and VLDL are large, triglyceride-rich lipoprotein particles that remain suspended in plasma, scattering light and making the sample appear milky or turbid.

• Chylomicrons especially cause creamy supernatant after standing due to their large size and buoyancy.

• VLDL causes uniform turbidity when elevated (e.g., in hypertriglyceridemia).

Why can't we distinguish between chylomicrons and VLDL in a lipemic (milky) blood sample after a patient has eaten?

In a non-fasting patient, both chylomicrons (from dietary fat) and VLDL (endogenously produced) may be elevated, contributing to lipemia. However:

• Chylomicron levels depend on time since the last meal—they usually clear within 8–12 hours, so persistent elevation suggests delayed clearance or a recent meal.

• VLDL is always present and can be elevated in metabolic conditions (e.g., insulin resistance).

• Both particles are triglyceride-rich and compete for lipoprotein lipase (LPL), which clears them from circulation. This competition may delay clearance of both.

What triglyceride (TAG) levels are considered elevated?

• Normal: < 150 mg/dL

• Borderline high: 150–199 mg/dL

• High: 200–499 mg/dL

• Very high: ≥ 500 mg/dL

What is familial hypercholesterolemia(FH), and what is its:

• Cause

• Result

• Treatment

• It is caused by a LDL clearance defect

• Leads to accumulation of LDL cholesterol, and can cause xanthomas

• Statins inhibit HmG CoA Reductase, reducing cholesterol so LDL receptors uptake more LDL to get the cholesterol and lower blood cholesterol

What is a xanthoma

Cholesterol deposits due to LDL leakage into tissues in tendons like the achilles

What is secondary hypertriglyceridemia, and what is its:

• Cause

• Result

• Treatment

• Insulin resistance in diabetes, leading to dropped LPL activity(so less TG clearance) and no more inhibited lipolysis, so FFAs would increase leading to more VLDL

• High triglyceride and milky serum

• Fibrates break down triglyceride