Lipid Metabolism

Question 1

Adverse endocrine effects of adipose tissue

Answer 1

incr SNS, incr resistin (insulin resistance), incr leptin –> incr appetite, incr FA’s–> incr atherosclerosis, incr AT, incr inflammatory mediators

Question 2

How does increased adiposity contribute to insulin resistance and dyslipidemia?

Answer 2

With insulin resistance, hormone sens lipase is inhibited and results in the release of FFA’s and glycerol from adipose that goes to the liver. In liver, glycerol converted to glucose via GNG. FFAs converted to VLDL for subsequent conversion to LDL via LPL or HTGL or small HDL and LDL via CETP or HTGL.

Question 3

Effects of Niacin on lipid metabolism

Answer 3

Decr VLDL production by blocking VLDL production in liver by inhibiting VLDL synthesis by inhibiting DAG acyltransferase 2. Reduces lipolysis from adipocytes. Reduces apo A-1 catabolism, but cholesterol can still be removed from HDL

Question 4

Major effects of Niacin

Answer 4

incr HDL by 15-30%, reduces TG by 20-50%, reduces LDL by 10-30%. Modest evidence of CVD reduction when monotherapy, ltd effect when combine w/ statins or side fx.

Question 5

Side effects of niacin

Answer 5

flushing, itching, abdominal pain, ulcers, insulin resistance, hepatotoxicity, gout, myalgia/myopathy (esp w/ statins).

Question 6

Effects of fibrates

Answer 6

1. decr VLDL production in liver 2. incr lipolysis

reduces TG by 20-50%, incr HDL by 10-20%, reduce LDL by 5-20%.

Question 7

Mechanism of action of fibrates

Answer 7

activates PPAR-alpha for synthesis of apo A-1 and A-2, activates LPL and reduces apo C3 (LPL inhibitor), stim hepatic FA uptake and catabolism by beta-oxidation to reduce TG synthesis.

Question 8

Side effects of fibrates

Answer 8

abdominal pain, gall stones, incr creatinine, myalgia/myopathy (esp. w/ statins).

Question 9

Lipid effects of Omega-3 FAs (Fish Oils)

Answer 9

dose-dep (need >3-4 g/day) to reduce TG by 20-50%, modest effects on HDL (related to TG reduction), LDL may incr or not change. Mild platelet effects.

Question 10

Mechanism of action of Omega-3 FA’s.

Answer 10

inhibit DGAT, reduces lipolysis, stim hepatic FA catabolism by beta-oxidation–> reduces TG synthesis.

Question 11

Side effects of Omega-3 FAs

Answer 11

eructiation, flatulence, abdominal pain, bruising and bleeding (from mild platelet effects).

Question 12

What categorizes a pt as high CVD risk based on lipid goals?

Answer 12

established CVD (CHD, PAD, stroke), LDL >190 mg/dL, TG >500 mg/dL

Question 13

Sequence of lipid therapy based on lipid pattern?

Answer 13

All need lifestyle changes.
TG >200 mg/dL: 1. statin, 2. add ezetimibe or BAS, 3. niacin, BAS, or ezetimibe
TG 200-499 mg/dL: 1. statin, 2. add ezetimibe, 3. add niacin
TG >500 mg/dL: 1. niacin, fish oil, or fibrate, 2. combine niacin, fish oils, or fibrate, 3. add third TG-lowering drug, consider adding a statin.