Regulation of Body Mass, Metabolic Syndrome, and Type II Diabetes

Question 1

What are the effects of increased glucose post-prandial?

Answer 1

Increased glycolysis and glycogenesis

Question 2

What happens 2 hours post-prandial?

Answer 2

• Glucose decreases

- Liver glycogen releases glucose (glucagon)

Question 3

What happens 4 hours post-prandial?

Answer 3

• More glucagon is secreted
• More TG hydrolysis
• FA becomes the major fuel

Question 4

What happens to non-essential amino acids in prolonged fasting?

Answer 4

They are deaminated

Question 5

Which proteins are preferentially depleted in the liver and heart?

Answer 5

Lys-Phe-Glu-Arg-Gln

Question 6

In prolonged fasting, what happens to oxaloacetate?

Answer 6

• Diverted to gluconeogenesis

- Prevents Acetyl-CoA entry into the TCA cycle –> accumulation of Acetyl-CoA

Question 7

What is oxidized as fuel during prolonged fasting?

Answer 7

Fatty acids, produces Acetyl-CoA

Question 8

What does an accumulation of Acetyl-CoA during prolonged fasting lead to?

Answer 8

Favors ketone body synthesis

Question 9

What is the main difference between a normal weight person and an obese person’s stores?

Answer 9

More adipose tissue for obese people (better hibernation, fasting)

Question 10

How long can someone survive fasting if hydrated?

Answer 10

30 to 40 days

Question 11

When do severe symptoms appear after fasting? When does death occur? Due to what?

Answer 11

• Symptoms: 35 to 40 days
• Death: 40 to 61 days
• Organ failure or myocardial infarction

Question 12

What do people die from during starvation?

Answer 12

• Not from starvation/lack of nutrients

- Infectious diseases due to a weakened immune system

Question 13

Differentiate Type 1 and Type 2 diabetes.

Answer 13

• Type 1: insufficient production of insulin (problem in insulin concentration)
• Type 2: insulin resistance (problem in insulin signaling)

Question 14

What is the cause of Type 1 diabetes?

Answer 14

• Usually due to an autoimmune destruction of B-cells

- Usually develops early in life (childhood diabetes)

Question 15

What is the cause of Type 2 diabetes?

Answer 15

B-cells work so hard, that they eventually give up and do not respond appropriately to insulin

Question 16

What is elevated in diabetes? What is the consequence?

Answer 16

• Blood glucose
• Increased osmolality
• Excessive urination and thirst

Question 17

What is the consequence on proteins due to glucose abnormalities?

Answer 17

Proteins get glycosylated, which leads to abnormal functions

Question 18

What happens in Type I diabetes? What are the consequences?

Answer 18

• Fat breakdown is accelerated, which leads to an increase in ketone bodies
• Increase in blood (H+) leads to ketoacidosis

Question 19

What does ketoacidosis activate in Type I diabetes? What does that lead to?

Answer 19

• Bicarbonate buffering system is activated, which leads to altered breathing patterns
• Breakdown of acetoacetate produces acetone, which is expelled via the breath

Question 20

What does untreated Type I diabetes lead to?

Answer 20

• Dramatic weight loss

- Breakdown of proteins and lipids as an energy source

Question 21

What hormones does adipose tissue release?

Answer 21

• Peptide hormones called adipokines

- Carry information about fuel stores to the brain

Question 22

What are orexigenic neurons?

Answer 22

Increase appetite and eating behaviour

Question 23

What are anorexigenic neurons?

Answer 23

Decrease appetite by inducing satiety

Question 24

What are the consequences of leptin?

Answer 24

Activates a-MSH, which activates anorexigenic neurons (less eating)

Question 25

What are the consequences of insulin?

Answer 25

Inactivates NPY, which inactivates orexigenic neurons (less eating)

Question 26

What are the consequences of ghrelin?

Answer 26

Activates NPY, which activates orexigenic neurons (more eating)

Question 27

What are the consequences of satiety signals, such as PYY?

Answer 27

Inactivates NPY, which inactivates orexigenic neurons (less eating)

Question 28

What happened to homozygous ob/ob mice?

Answer 28

- Ate continually | - Obese, elevated cortisol, shivered, infertile, insulin resistance, died early

Question 29

What happened to homozygous ob/ob mice when leptin was injected?

Answer 29

The mice lost weight and temperature returned to normal

Question 30

Why does leptin administration to obese people not restore normal body mass?

Answer 30

- Since they have higher levels of leptin | - Theory of leptin resistance

Question 31

What are db/db mice? What does the db gene encode for?

Answer 31

- Obese and diabetic | - db gene encodes the leptin receptor (Lepr) in the brain, and is mostly expressed in the hypothalamus

Question 32

Where is ghrelin secreted? Where are the ghrelin receptors?

Answer 32

- Secreted from the stomach | - Receptors: brain, heart, adipose tissue

Question 33

How does ghrelin work? What is the consequence of injecting ghrelin?

Answer 33

- Works via GPCR to increase the sensation of hunger | - Injection of ghrelin immediately increases appetite

Question 34

What is PYY?

Answer 34

- Appetite-suppressing hormone | - Peptide with 36 AA with two Tyrosine (Y) residues at the end

Question 35

Where is PYY secreted from? What does it activate/inhibit? What is the result

Answer 35

- Secreted from the small intestine and colon - Inhibits the release of orexigenic NPY neurons - Results in reduced hunger

Question 36

What are most bacterial products?

Answer 36

Short-chain FA: acetate, propionate, butyrate

Question 37

What is the consequence of propionate?

Answer 37

- Acts through GPCR 43 and 41 - Stimulates adipocyte differentiate - Inhibits lipolysis - Fat is not hydrolyzed, and accumulates in adipose tissue

Question 38

Some microorganisms create __________ that affect adipose tissue

Answer 38

fermentation products

Question 39

What do enlarged adipocytes produce?

Answer 39

Macrophage chemotaxis protein (MCP-1)

Question 40

What is the effect of MCP-1?

Answer 40

Attracts macrophages, which infiltrate adipose tissue

Question 41

What is the effect of macrophage infiltration?

Answer 41

- Exports fatty acids to muscle - Interferes with GLUT4 (insulin-sensitive) - Produces insulin resistance (Type II diabetes)

Question 42

How does insulin resistance lead to the accumulation of fat?

Answer 42

- If glucose is not utilized, it is stored as glycogen | - But, since there is a limit for glycogen storage, excess glucose is converted to fatty acids

Question 43

Which would be most important to produce sugars required in high concentrations for mitosis? ``` A) Pentose phosphate, oxidative B) Gluconeogenesis C) Lactate fermentation D) Pentose phosphate, non-oxidative E) None would contribute the specific sugars required in advance of mitosis ```

Answer 43

A) Pentose phosphate, oxidative phase

Question 44

What product of the preparatory phase of glycolysis is required in the payoff phase, but at twice the concentration? A) DHAP B) Pyruvate C) NAD+ D) ADP

Answer 44

D) ADP

Question 45

Which of the following strategies is NOT actually applied in the coordinated regulation of glucose metabolism? A) A change in the expression of metabolic enzymes B) An allosteric change in the activity of metabolic enzymes C) A change in the cellular location of existing metabolic enzymes D) Phosphorylation or dephosphorylation of an enzyme in a metabolic pathway E) All of the above strategies in cells function to regulate glucose metabolism

Answer 45

E) All of the above strategies in cells function to regulate glucose metabolism