L9 Lipid Metabolism and Dyslipidemia

Question 1

Size of Lipoproteins?

Answer 1

HDL< LDL < IDL< VLDL < Chylomicrons

Question 2

_______________: Modified atherogenic LDL w/ Apo (a), most atherogenic lipoprotein

Answer 2

Lipoprotein A: Modified atherogenic LDL w/ Apo (a)

most atherogenic lipoprotein

Question 3

What is an important biomarker for increasded CVD risk?

Answer 3

Apo (a) is an important biomarker and indicator CVD risk

measure someone once if high -> increased CVD risk

Question 4

What is an important biomarker for increasded CVD risk?

Answer 4

Apo (a) is an important biomarker and indicator CVD risk

measure someone once if high -> increased CVD risk

Question 5

______________:

Absorb dietary triglycerides, some cholesterol

Transports to peripheral tissues and liver

Answer 5

Chylomicrons (ApoB48, ApoE and Apo C-II)

Absorb dietary triglycerides, some cholesterol

Transport to peripheral tissues and liver

Question 6

______________:

TG-rich

Transport TG and chol around the body –> LDL as they lose Triglycerides

Answer 6

VLDL (ApoB-100 , ApoE and Apo C-II)

TG-rich

Transport TG and chol around the body.

VLDL –> LDL as they lose Triglycerides

Question 7

___________:

Carries cholesterol in its core to peripheral tissues

Targetted by Statins

Pathogenesis?

Answer 7

LDL (ApoB-100)

Carries cholesterol in its core to peripheral tissues

Pathogenesis:

HIGHER LDL => Increased risk of CVD

LDL is difficult to be taken up by macrophages → atherotic lesions

Modification of LDL (Primarily through oxidation)

Smoking increases oxidation

Once modified more easily taken up

Question 8

How do Statins function?

Answer 8

LDL receptor in the liver is key one for lipoprotein metabolism

statins upregulate LDL receptor in liver

=> clears LDL from circulation

Question 9

____________:

Carries cholesterol from peripheral to liver

excretion in bile or feces

Known as Reverse Cholesterol transport

Answer 9

HDL (ApoA-I, ApoA-II, ApoE, Apo C-II)

Carries cholesterol from peripheral to liver

excretion in bile or feces

Known as Reverse Cholesterol transport

LOWER HDL => Increased risk of CVD

Question 10

LOWER ________ and HIGHER ________ => Increased risk of CVD

Answer 10

LOWER HDL** and HIGHER **LDL => Increased risk of CVD

Question 11

Role of cholesterol in the body?

How is it regulated?

Answer 11

Cholesterol is used for steroid hormone synthesis and cell wall synthesis.

Cannot be metabolized, only secreted!!

Increased fiber content of diet –> promotes cholesterol secretion in feces

Question 12

____________ celaves lipoproteins for circulation during endogenous lipoprotein metabolism

Answer 12

APO C II

(Chylomicrons and VLDL)

Question 13

_________ potent at driving endogenous cholesterol synthesis

Answer 13

Saturated fats potent at driving endogenous cholesterol synthesis

Question 14

________ and ________ interact with lipoprotein receptors as part of endogenous lipoprotein metabolism

Answer 14

APO E and APO B interact with lipoprotein receptors as part of endogenous lipoprotein metabolism

Question 15

Familial Hypercholesterolemia Types?

Answer 15

ApoC-II or LPL defect (Type I): Hyperchylomicronemia

=> excessive accumulation of chylomicrons

LDL receptor defect (Type II)

Very hard to treat (Most LDL treatments target LDL receptor expression)

Treat w/ apheresis to filter out excess LDL every few weeks

ApoE defect (Type III)

Question 16

ApoB-48 is associated with which Lipoproteins?

Answer 16

Chylomicrons

Question 17

ApoB-100 is associated with which Lipoproteins?

Answer 17

VLDL

IDL

LDL

Question 18

ApoA is associated with which Lipoproteins?

Answer 18

HDL

Question 19

ApoE is associated with which Lipoproteins?

Answer 19

Chylomicrons

vLDL

HDL

Question 20

ApoC is associated with which Lipoproteins?

Answer 20

Chylomicrons

VLDL

HDL

Question 21

Endogenous Pathway of Lipoprotein Metabolism

Answer 21

Majority of Cholesterol from this

Question 22

Exogenous pathway of Lipoprotein Metabolism

Answer 22

Exogenous Pathway: taking in from external source

Food eaten –> triglycerides –> cholesterol

Not much cholesterol eaten, when it is upregulated enzymes that break it down

Question 23

The blood of a person who consumes large amounts of animal fat would most likely contain which one of the following soon after consumption?

A.Increased levels of LDL and HDL

B.Increased levels of HDL

C.Increased levels of VLDL

D.Increased levels of VLDL and HDL

E.Increased levels of chylomicrons

Answer 23

The blood of a person who consumes large amounts of animal fat would most likely contain which one of the following soon after consumption?

A.Increased levels of LDL and HDL

B.Increased levels of HDL

C.Increased levels of VLDL

D.Increased levels of VLDL and HDL

E.Increased levels of chylomicrons

Question 24

Hyperchylomicronemia: (__________ or ___________ defect)

=> excessive accumulation of chylomicrons

Answer 24

Hyperchylomicronemia:Type I- (ApoC-II**or**Lipoprotein Lipase (LPL) Defect)

=> excessive accumulation of chylomicrons

Question 25

Answer 25

Question 26

Dyslipidemia in Diabetes

Answer 26

**_Increased_**: TG VLDL LDL Apo B **_Decreased_**: HDL Apo A I

Question 27

Clinical Manifestations of Dyslipidemia?

Answer 27

**Xanthoma** (cholesterol deposits in skin/tendons/joints) **Xanthelasma** (yellow plaque on eyelids-excess cholesterol) **Lipemia Retinalis** (milky retina -excess Chylomicron/TG) **Atherosclerosis**

Question 28

Primary vs. Secondary Management of CVD Risk

Answer 28

**_Primary prevention_** aimed at people who already have developed cardiovascular risk factors, such as high blood pressure or high cholesterol =\> to prevent progression to CVD **_Secondary Prevention_** preventing heart attack and stroke through drug therapy and counseling for high-risk individuals– those with previous events or known CVD

Question 29

Strategies to Lower LDL Cholesterol Levels?

Answer 29

Avoid dietary trans fat Reduce Saturated Fats Increase Fiber Intake

Question 30

**\_\_\_\_\_\_\_\_\_\_\_\_\_** blocks reabsorption of both biliary and dietary cholesterol from intestine

Answer 30

**Ezetimibe** blocks reabsorption of both biliary and dietary cholesterol from intestine

Question 31

\_\_\_\_\_\_\_\_\_\_\_\_\_\_ block reabsorption of bile-acids into circulation

Answer 31

**Bile-acid sequestrants** block reabsorption of bile-acids into circulation

Question 32

\_\_\_\_\_\_\_\_\_\_ represents ~25% of total cholesterol in intestine \_\_\_\_\_\_\_\_\_\_ represents ~75% of total cholesterol in intestine

Answer 32

**Dietary cholesterol** represents ~25% of total cholesterol in intestine **Biliary cholesterol (Liver)** represents ~75% of total cholesterol in intestine

Question 33

Intestinal cholesterols absorbed by \_\_\_\_\_\_\_\_\_ =\> returned to the liver =\>repackaged with \_\_\_\_\_\_\_\_\_

Answer 33

Intestinal cholesterols absorbed by **chylomicrons** =\> returned to the liver =\>repackaged with **apoB-100** =\> from **VLDL**

Question 34

A patient with a hyperlipoproteinemia would be most likely to benefit from a low-carbohydrate diet if the lipoproteins that are elevated in the blood belong to which class of lipoproteins? A.LDL B.VLDL C.Chylomicrons D.Chylomicrons and VLDL E.HDL

Answer 34

A patient with a hyperlipoproteinemia would be most likely to benefit from a low-carbohydrate diet if the lipoproteins that are elevated in the blood belong to which class of lipoproteins? A.LDL **B.VLDL** C.Chylomicrons D.Chylomicrons and VLDL E.HDL

Question 35

Factors influencing HDL Levels?

Answer 35

**Factors that increase HDL** –Oral estrogens –Aerobic exercise –Alcohol intake **Factors that decrease HDL** –Low-fat, high-carbdiets –Obesity –Metabolic Syndrome/Hypertriglyceridemia –Type II diabetes –Androgens, some progestins –Beta-blockers

Question 36

\_\_\_\_\_\_\_\_\_ is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight.

Answer 36

**_Metformin_** is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight.

Question 37

Which one of the following is characteristic of high-density lipoprotein? A. It carries apolipoproteinE, an activator of lipoprotein lipase B. It is produced by the action of lipoprotein lipase on VLDL C. It is digested by muscle lysosomes D. Its major apolipoproteinis apoB48 E. It is remodelled by cholesterol ester transfer protein

Answer 37

Question 38

**REDUCED ______ ASSOCIATED W/ HYPERTRIGLYCERIDEMIA**

Answer 38

**REDUCED _HDL_ ASSOCIATED W/ HYPERTRIGLYCERIDEMIA**