Lipid Metabolism

Question 1

Briefly describe the exogenous lipid pathway

Answer 1

Dietary lipids enter the small intestine and are bound by chylomicrons containing ApoC, ApoE, ApoB-48, etc. and these travel through the intestine where LPL strips free fatty acids (which then go to muscle and adipose tissue). The smaller remnant chylomicron (atherogenic) then goes to the liver and is taken up via the LDL receptor.

Question 2

Briefly describe the endogenous lipid pathway

Answer 2

Chylomicron (10:1 TG:CHOL) remnants deliver fatty acids, etc. to the liver where they are re-esterified into TAGs and then packaged into VLDL (5:1 TG:CHOL) containing ApoB-100, ApoE, and ApoC that transports it to the body from the liver.

Question 3

What is IDL?

Answer 3

Intermediate density lipoprotein (1:1 TG:CHOL) which is made after fatty acids and some cholesterol are stripped off endogenous VLDL. Contains ApoB-100 and ApoE but ApoC has been stripped. This is highly atherogenic as well

Question 4

What happens to IDL?

Answer 4

it is acted upon by hepatic lipase and the remaining TAGs are stripped leaving a cholesterol rich LDL (less than 5% TAG) molecule.

Question 5

What is the role of HDL?

Answer 5

to transport cholesterol back to the liver to complete the cycle

Question 6

What happens if too much LDL is circulating?

Answer 6

some is taken up by peripheral tissue like vessel walls causing atherosclerosis

Question 7

Write out the Friedewald Formula.

Answer 7

LDL = TC - HDL - TG/5.0 (mg/dL)

Question 8

What does ApoCII do?

Answer 8

cofactor for lipoprotein lipase (LPL)

Question 9

What does ApoCIII do?

Answer 9

inhibits LPL so high levels leads to hypertriglyceridemia

Question 10

What is primary chylomicronemia?

Answer 10

defective removal of CM caused by a apoCII or LPL defect leading to elevated levels of chylomicrons, VLDL elevation, and pancreatitis (common anytime VLDL gets over 1000)

Question 11

What is the treatment for primary chlyomicronemia?

Answer 11

take the fat out of the diet and replace with medium chain fats that can be broken down without chylomicrons

Question 12

What is familial hypertriglyceridemia?

Answer 12

defective metabolism of VLDL (LPL defect common) leading to elevated VLDL, pancreatitis, hyperTAG

Question 13

What is familial dysbetalipoproteinemia?

Answer 13

defective metabolism of VLDL via ApoE defect (activates hepatic lipase) (E2/E2 alleles) in which VLDL can be metabolized to IDL but the IDL then sticks and cant be metabolized cholesterol and TAG will both be increased

Question 14

What does familial dysbetalipoproteinemia lead to?

Answer 14

elevated VLDL, IDL, and CM remnants leading to elevated cholesterol and atherosclerosis

Question 15

How is familial dysbetalipoproteinemia tested?

Answer 15

give the patient a statin which usually lowers LDL but these patients don’t have much LDL so nothing happens

Question 16

What is familial combined hyperlipidemia (FCH)?

Answer 16

overproduction of apoB-100 so VLDL is being pumped out too quick and both VLDL and LDL become elevated leading to premature atherosclerosis

Question 17

MOI of FCH?

Answer 17

AD

Question 18

What is familial hypercholesterolemia (FH)? Are TAG levels elevated?

Answer 18

LDL receptor or ApoB defect leading to decreased receptor levels so LDL cannot be cleared effectively leading to high cholesterol hyperTAGemia is not invariably present (TAGs should be normal here)

Question 19

What should total cholesterol levels be?

Answer 19

less than 200 mg/dL

Question 20

What should LDL cholesterol levels be?

Answer 20

less than 130 mg/dL

Question 21

What should TAG levels be?

Answer 21

less than 120 mg/dL

Question 22

What should HDL levels be in men? women?

Answer 22

greater than 40 for mengreater than 50 for women

Question 23

What are some secondary causes of hyperlipidemia?

Answer 23

-hypothyroidism-kidney disease (nephrotic)-liver disease (hepatitis, biliary disease)-medications-obesity-simple sugars

Question 24

Why would nephrotic syndrome lead to hyperlipidemia?

Answer 24

albumin suppresses VLDL production

Question 25

What kinds of meds could cause hyperlipidemia?

Answer 25

-estrogen (increases TAGs)-b-blockers -thiazide diuretics

Question 26

What do high doses of b-blockers and thiazide diuretics do?

Answer 26

block the function of lipoprotein lipase and increase TAG levels

Question 27

What are the principle dietary factors that increase LDL?

Answer 27

cholesterol and saturated and trans-fats (red meat, dairy products, cheese, pastries, baked goods)

Question 28

What does HDL do?

Answer 28

binds to ABCG1 transporter on the surface of macrophages and loads cholesterol onto itself and transports it back to the liver in a process called ‘reverse cholesterol transport’