Diseases of lipid metabolism

Question 1

What is atherosclerosis?

Answer 1

Atherosclerosis is the formation of fatty plaques within the vessel walls. They start with the deposition of cholesterol into the vessel wall by LDL, before macrophages eat it and form foam cells. These foam cells then start an inflammatory response and cause the coagulative system to be activated. The plaque develops from then. Smooth muscle cells also undergo changes to become fibroblasts that also produce lots of extracellular matrix in the vessel lumen.

Question 2

What is hypercholesterolaemia and how is it prevented in the body?

Answer 2

Hypercholesterolaemia is the build-up of cholesterol in the bloodstream. This is very dangerous. Thus, LDL and VLDL transporters work to remove it from the bloodstream and deposit it into the vessels.

Question 3

What is familial hypercholsterolaemia?

Answer 3

Familial hypercholesterolaemia is a hereditary condition in which mutations to the LDL cellular receptor inhibits cellular uptake of cholesterol from the blood.

Question 4

There are many different types of mutations that can occur to inhibit the LDL cholesterol uptake pathway. Where can these mutations take place?

Answer 4

Mutations to the cholesterol uptake process can occur:

1. No detectable LDL precursor - failure in expression
2. Poor precursor processing
   - failure to move to the cell surface.
3. Abnormal ligand binding
   - inability to bind LDL.
4. Defective internalization - failure to degrade LDL

Question 5

Is familial hypercholesterolaemia autosomal dominant or recessive?

Answer 5

It can be both. The degree of hypercholesterolaemia is proportional to whether the mutation is in both LDL alleles or just one of them.

Question 6

What is the fatality associated with familial hypercholesterolaemia?

Answer 6

Homozygous (autosomal recessive): 100% fatal before the age of 15.
Heterozygous (autosomal dominant): myocardial infarction in 75% in males and 45% in females.

Question 7

How do Statin drugs work to reduce LDL cholesterol?

Answer 7

Statin drugs are inhibitors of the enzyme HMG CoA reductase, which converts melanovate into cholesterol. Statin drugs also upregulate expression of the LDL receptor on the liver cells, so that it can be taken up there.

Question 8

What was the North Karelia project conducted by Dr Puska?

Answer 8

He wanted to prove that CVD risk factors like smoking, high fat diet and high blood pressure all contributed to the high CVD mortality in East Finland. He ordered a ban on smoking and high fats and blood pressure was reduced. He was able to reduce the CVD mortality by 73%.

Question 9

What is Tangier’s disease?

Answer 9

Tangier’s disease is a mutation in the ABCA 1 transporter gene. ABCA 1 is a key element in reverse cholesterol transport, regulating the removal of cholesteryl ester from the tissues into the empty ApoA-1 transporters, soon to become premature HDL.

Question 10

What occurs as a result of Tangier’s disease?

Answer 10

There is no HDL production and no reverse cholesterol transport. This results in increased CVD risk and even cholesterol deposition in the tonsils!

Question 11

What is the suggested relationship between high cholesterol levels and Alzheimer’s disease?

Answer 11

Well, Alzheimer’s disease is the aggregation of Amyloid precursor protein, or hyperphosphyralted tau proteins. However, this aggregation can only occur in special lipid rafts within the nucleus. The higher the cholesterol levels, the higher the abundance of the lipid rafts. Thus, it is proposed that if cholesterol levels are low, there won;t be enough rafts in the neurons to facilitate aggregation of the tau proteins.

Question 12

What is metabolic syndrome?

Answer 12

This is basically when your increased body fat levels start to interfere with your body’s metabolism of energy. To have metabolic syndrome, one must have abdominal obesity in conjuction with high BP, insulin resistance, high blood lipid levels. They must also be in a proinflammatory and prothrombotic state.

Question 13

Is metabolic syndrome associated with a particular age group?

Answer 13

Metabolic syndrome is associated with people over 50.

Question 14

How does excess body fat promote a proinflammatory state that contributes to metabolic syndrome?

Answer 14

Excess body fat actually triggers an immune response, inducing low level systemic inflammation of the adipose tissue. Thus, the body fat increases the amount of inflammatory cytokines throughout the body.

Question 15

How does insulin resistance contribute to metabolic syndrome?

Answer 15

Insulin resistance alters metabolism because the insulin receptors on the cells throughout the body (muscle and adipose) become desensitised and stop working. This will eventually lead to full diabetes onset.

Question 16

Losing weight is not so hard. Maintaining the weight loss is difficult. What is the physiological process for this?

Answer 16

The hypothalamus and brain centres that regulate metabolism and energy expenditure have the ability to either increase metabolism when there is lots of nutrition available or decrease metabolism when nutrition is low. The brain knows our normal weight, and if we deviate from it through weight loss, then our body thinks we are starving. So, it decreases our anabolic processes that consume energy and increase our catabolic processes that provide energy. This will enable weight management.

Question 17

Anabolic pathways have what effect on the body?

Answer 17

These pathways consume energy and are associated with the production of important molecules the body needs. These pathways are inhibited during fad diets, to reduce energy expenditure and return to normal weight.

Question 18

Catabolic pathways have what effect on the body?

Answer 18

These pathways produce energy and are associated with the breakdown of energy-rich molecules the body needs. These pathways are increased during fad diets, to induce energy expenditure and return to normal weight.