DHN 311 FINAL EXAM QUESTIONS
WITH ALL CORRECT ANSWERS
Where are macrophages and foam cells derived from? - Answer-- Macrophages:
Derived from monocytes (which are leukocytes)
- Foam cells: Derived from macrophages that have ingested oxidized LDL
What is the significance of scavenger receptors? - Answer-- NOT down-regulated in
response to intracellular cholesterol
- Continue to engulf cholesterol rich particles until they transform into foam cells (may
proliferate to form plaque)
What comprises a fibrous cap? - Answer-- Smooth muscle
- Elastin
- Collagen
How does the necrotic core form? - Answer-- Macrophages and monocytes die
At what point is a clot considered to be formed? - Answer-- Ruptured fibrous cap;
plaque seeps into the blood vessel
- Tissues have died; fibrous cap is either stable or unstable
- Unstable fibrous cap can increase the risk of CVD
What role does HDL have in modifying plaque formation and development? - Answer-
HDL involved in reverse cholesterol transport and has anti-inflammatory actions
How do saturated fats, trans fats, and cholesterol contribute to the risk of
atherosclerosis? - Answer-1) Inhibition of LDL receptor activity
2) Adipose tissue inflammation by activating pathways that turns on inflammatory
cytokines
3) Activate macrophages to increase the release of cytokines
Saturated Fats:
- Indirectly increasing the expression of a number of inflammatory genes in adipocytes
by a nuclear factor kappa B mechanism
- Directly stimulating inflammatory molecules in macrophages. Macrophages recruited
into adipose tissue by SFAs have been shown to secrete TNFa's which further
aggravates adipose tissue inflammation.
What is insulin resistance and how are serum insulin and glucose levels reflected in this
state? - Answer-- IR - decreased ability of target tissues (liver, muscle & adipose) to
, respond properly to normal/elevated circulating concentrations of insulin, characterized
by uncontrolled hepatic glucose production, and decreased glucose uptake by muscle
and adipose tissue
- Serum insulin levels - increased
- Serum glucose levels - increased
What effect does insulin have on adipose, liver, and muscle tissues under normal and
abnormal conditions (insulin resistance) (be specific regarding which pathways are
turned on, the activity of hormone sensitivity lipase, lipoprotein lipase, and the activity of
GLUT 4 receptors)? - Answer-Normal - decrease HSL, increase LPL, promotes
recruitment of GLUT 4
Muscle: increase glucose transport, glycogenesis, protein synthesis
Liver: decrease gluconeogenesis & glycogenolysis, increase glycogenesis
Adipose: increase glucose transport, protein synthesis & lipogenesis, decrease lipolysis
Abnormal (IR) - increase HSL, decrease LPL, Increase blood glucose and decrease
GLUT 4 activity
Muscle: decrease glucose uptake
Liver: increase gluconeogenesis, increase glucose production, increase glycogen
breakdown
Adipose Tissue: increase lipolysis, increase FFA, increase ketogenesis
Why is insulin binding to its receptor and the resulting phosphorylation cascade critical
to lowering blood glucose levels to normal levels? - Answer-Phosphorylates insulin
receptor residues, which interact with each other and consequently phosphorylate
molecules that lead to the activation of several pathways that affect gene expression,
cell metabolism and growth.
What are the metabolic changes that occur that lead to lipotoxicity and glucotoxicity?
These are metabolic changes that you see with insulin resistance and diabetes. READ
PAGE 167 - Answer-- Lipotoxicity - excessive deposition of lipid in muscle & liver (non-
adipose tissue), increases risk of type 2 diabetes
- Glucotoxicity - chronic hyperglycemia
How does inflammation arise in adipose tissue? - Answer-As adipocytes expand,
production of adipokines increase
Obese adipose tissue (hypertrophic adipocytes) is infiltrated by macrophages.
Macrophages and hypertrophic adipocytes cause release of adipokines (pro-
inflammatory).
After reviewing this section do you understand how obesity can lead to insulin
resistance due to hyperlipidemia/hyperglycemia and chronic inflammation? - Answer-
Weight gain increases fat cell number & fat cell size, leading to hypertrophied fat cells
(over sized), which do not respond well. Hypertrophied adipocytes have increased
cytokine release (promotes inflammation which is increased risk of atherosclerosis) and
increase the release of free fatty acids. Cytokine release and free fatty acid release
WITH ALL CORRECT ANSWERS
Where are macrophages and foam cells derived from? - Answer-- Macrophages:
Derived from monocytes (which are leukocytes)
- Foam cells: Derived from macrophages that have ingested oxidized LDL
What is the significance of scavenger receptors? - Answer-- NOT down-regulated in
response to intracellular cholesterol
- Continue to engulf cholesterol rich particles until they transform into foam cells (may
proliferate to form plaque)
What comprises a fibrous cap? - Answer-- Smooth muscle
- Elastin
- Collagen
How does the necrotic core form? - Answer-- Macrophages and monocytes die
At what point is a clot considered to be formed? - Answer-- Ruptured fibrous cap;
plaque seeps into the blood vessel
- Tissues have died; fibrous cap is either stable or unstable
- Unstable fibrous cap can increase the risk of CVD
What role does HDL have in modifying plaque formation and development? - Answer-
HDL involved in reverse cholesterol transport and has anti-inflammatory actions
How do saturated fats, trans fats, and cholesterol contribute to the risk of
atherosclerosis? - Answer-1) Inhibition of LDL receptor activity
2) Adipose tissue inflammation by activating pathways that turns on inflammatory
cytokines
3) Activate macrophages to increase the release of cytokines
Saturated Fats:
- Indirectly increasing the expression of a number of inflammatory genes in adipocytes
by a nuclear factor kappa B mechanism
- Directly stimulating inflammatory molecules in macrophages. Macrophages recruited
into adipose tissue by SFAs have been shown to secrete TNFa's which further
aggravates adipose tissue inflammation.
What is insulin resistance and how are serum insulin and glucose levels reflected in this
state? - Answer-- IR - decreased ability of target tissues (liver, muscle & adipose) to
, respond properly to normal/elevated circulating concentrations of insulin, characterized
by uncontrolled hepatic glucose production, and decreased glucose uptake by muscle
and adipose tissue
- Serum insulin levels - increased
- Serum glucose levels - increased
What effect does insulin have on adipose, liver, and muscle tissues under normal and
abnormal conditions (insulin resistance) (be specific regarding which pathways are
turned on, the activity of hormone sensitivity lipase, lipoprotein lipase, and the activity of
GLUT 4 receptors)? - Answer-Normal - decrease HSL, increase LPL, promotes
recruitment of GLUT 4
Muscle: increase glucose transport, glycogenesis, protein synthesis
Liver: decrease gluconeogenesis & glycogenolysis, increase glycogenesis
Adipose: increase glucose transport, protein synthesis & lipogenesis, decrease lipolysis
Abnormal (IR) - increase HSL, decrease LPL, Increase blood glucose and decrease
GLUT 4 activity
Muscle: decrease glucose uptake
Liver: increase gluconeogenesis, increase glucose production, increase glycogen
breakdown
Adipose Tissue: increase lipolysis, increase FFA, increase ketogenesis
Why is insulin binding to its receptor and the resulting phosphorylation cascade critical
to lowering blood glucose levels to normal levels? - Answer-Phosphorylates insulin
receptor residues, which interact with each other and consequently phosphorylate
molecules that lead to the activation of several pathways that affect gene expression,
cell metabolism and growth.
What are the metabolic changes that occur that lead to lipotoxicity and glucotoxicity?
These are metabolic changes that you see with insulin resistance and diabetes. READ
PAGE 167 - Answer-- Lipotoxicity - excessive deposition of lipid in muscle & liver (non-
adipose tissue), increases risk of type 2 diabetes
- Glucotoxicity - chronic hyperglycemia
How does inflammation arise in adipose tissue? - Answer-As adipocytes expand,
production of adipokines increase
Obese adipose tissue (hypertrophic adipocytes) is infiltrated by macrophages.
Macrophages and hypertrophic adipocytes cause release of adipokines (pro-
inflammatory).
After reviewing this section do you understand how obesity can lead to insulin
resistance due to hyperlipidemia/hyperglycemia and chronic inflammation? - Answer-
Weight gain increases fat cell number & fat cell size, leading to hypertrophied fat cells
(over sized), which do not respond well. Hypertrophied adipocytes have increased
cytokine release (promotes inflammation which is increased risk of atherosclerosis) and
increase the release of free fatty acids. Cytokine release and free fatty acid release
