Obesity

Question 1

Do you need to know what the BMI classifications are

Answer 1

Yes

Question 2

Do you need to know what risk factors for obesity are?

Answer 2

Yes

Question 3

Do you need to now the prevalence of obesity - both globally and locally?

Answer 3

Yes

Question 4

Is there a genetic predisposition to obesity?

Does obesity tend to be monogenic or polygenic?

Answer 4

Polygenic

Question 5

4 genetic causes of obesity

Answer 5

Prader Willi syndrome
Leptin deficiency
Leptin receptor deficiency
FTO gene

Question 6

Prader Willi:

• Do you need to know what gene is mutated, and by what mechanisms?
• Do you need to know the symptoms of Prader Willi syndrome?
• Do you need to know the various ways that Prader Willi predisposes to obesity?
• One hormonal factor that predisposes those with Prader Willi to obesity?

Answer 6

YEs
YEs
Yes
Increased ghrelin levels

Question 7

Leptin deficiency

• Describe how it contributes to obesity
• Can it be cured with leptin replacement?
• Do you need to know rat studies?

Answer 7

Mutation in ob gene –> leptin not produced. Lack of satiety signal –> constantly hungry and eating –> obesity
Yes
Yes

Question 8

Leptin receptor mutations

• Can it be cured with leptin replacement?
• • Do you need to know rat studeis?

Answer 8

No

Yes

Question 9

Sometimes, are environmental factors needed to unmask genetic predisposition to obesity?

Answer 9

Yes

Question 10

Can set point be re established in children and adults? Implication?
Do you need to know study?

Answer 10

Only children - can reestablish weight trajectory.

Yes

Question 11

Do you need to know animal studies?

Answer 11

Yes

Question 12

What would you expect to happen when you increase energy expenditure vs what actually happens, and why?

Answer 12

Lose weight

Weight maintained - as compensatory increase in food intake

Question 13

Do you need to know how GWAS discovered FTO as an obesity susceptibility gene?
Do you need to know specific actions of FTO?
Do you need to know studies?

Answer 13

Yes
Yes
Yes

Question 14

Do you need to know

• Various brain nuclei involved in appetite
• Dual centre hypothesis - VMH and LH
• Is everything else in the visual diagram?

Answer 14

Yes
Yes
Yes

Question 15

Do you need to know the following aspects about metabolic syndrome:
-Definition/diagnosis
Risk factors
Consequences

Answer 15

Yes

Question 16

Is BMI assocaited with increased chronic illness risk and mortality

Answer 16

Yes

Question 17

Do you need to know the following about T2D:

• Prevalence
• Heritability
• Diagnosis

Answer 17

Yes

Question 18

Do you need to know about insulin resistance mechanisms in the liver, skeletal muscle and adipose tissue?

Answer 18

Yes

Question 19

Where does glucose uptake primarily occur, and what is the primary site of insulin resistance?

Answer 19

Skeletal muscle

Question 20

Describe the two phases of type 2 diabetes pathogensis

Answer 20

Insulin resistance occurs.

Initially, beta cells secrete more insulin to keep BGLs stable. But then beta cells undergo failure –> BGLs soar

Question 21

What 4 mechanisms contribute to insulin resistance?

Do you need to know these in detail?

Answer 21

Lipotoxicity
Inflammation
Altered endocrine signals
Mitochondrial dysfunction

Yes

Question 22

Do you need to know the classifications of physical activity intensity, in terms of metabolic equivalents of tasks?

Answer 22

Yes

Question 23

What is an active couch potato

Answer 23

People who are highly active byt highly sedentary

Question 24

What fraction of people worldwide are physically inactive? Are males or females more inactive?

Answer 24

1/4, generally females.

Question 25

Do you need to konw types of self reported and device based methods for measuring sedentary behaviour? Do self reported measures tend to under report?

Answer 25

Yes | Yes

Question 26

Do you need to know the health consequences of sedentary behaviour?

Answer 26

Yes

Question 27

What combination of activity vs sedentary behaviour results in highest risk of mortality?

Answer 27

Low activity, high sedentary

Question 28

Has COVID increased sedentary time and decreased physical activity time?

Answer 28

Yes

Question 29

What are the 4 mechanisms through which sedentary behaviour increases chronic illness risk? Do you need to know these?

Answer 29

Increased blood glucose Increased blood pressure Impaired vascular function REduced cerebral blood flow Yes

Question 30

Do you need to know the 3 studies?

Answer 30

Yes

Question 31

Do you need to know the guidelines

Answer 31

Yes

Question 32

what are the 3 components of energy expenditure?

Answer 32

Obligatory energy expenditure Physical activity Adaptive thermogenesis

Question 33

Obligatory energy expenditure is aka

Answer 33

resting energy expenditure | basal metabolic rate

Question 34

Is BMR correlated to lean (fat free) body mass? Do females have lower BMR than males? Does BMR decrease over the lifespan

Answer 34

Yes Yes Yes

Question 35

Is weight change in response to exercise genetically determined? Do you need to know the studies?

Answer 35

Yes

Question 36

Do you need to know the exercise requirements for clinically significant weight loss?

Answer 36

Yes

Question 37

Do you need to know the benefits of exercise beyond weight loss?

Answer 37

Yes

Question 38

What is non exercise adaptive thermogenesis?

Answer 38

Energy used during physical activities that don't involve volitional exercise

Question 39

What are the 2 sites of adaptive thermogenesis?

Answer 39

Brown adipose tissue | Skeletal muscle

Question 40

Brown adipose tussue: describe stimulus and response of adaptive thermogenesis

Answer 40

Stimulus: cold, food, energy stores Increases sympathetic output and NA release NA binds to B3 receptors on BAT Activates signalling cascade that releases FFA from lipid droplets; FFA causes conformational change in UCP1 - opens pore, releases heat.

Question 41

BAT: do you need to know studies?

Answer 41

Yes

Question 42

In skeletal muscle, describe the types of UCP proteins

Answer 42

Mainly UCP3, some UCP2

Question 43

Is UCP3 as effective as UCP2, and if not what counteracts this?

Answer 43

No, high skeletal muscle mass

Question 44

In addition to UCPs, what is the other pathway that contributes to thermogenesis in muscle? Do you need to know mechanism?

Answer 44

Calcium cycling, yes

Question 45

Do you need to know the interindividual variation in posture allocation - role in human obesity study?

Answer 45

Yes

Question 46

Do you need to mnow the location of the adipocyte types, and changes in location over the lifespan

Answer 46

Yes

Question 47

Do you need to know - Morphological differences between white and brown adipsoe - Developmental origin differences of white vs brown adipocytes - Browning and whitening of adipose tissues and mechanism

Answer 47

Yes Yes Yes

Question 48

After weight loss, what happens to - total energy expenditure - hunger signals - satiety signals - Do you need to know the studies?

Answer 48

Total energy expenditure decreases Satiety signals decrease Hunger signals increase

Question 49

Do you need to understand weight cycling? What happens to weight over time?

Answer 49

Yes, keeps increasing

Question 50

Do you need to know the mouse yoyo dieting study?

Answer 50

Yes

Question 51

Ketogenic diets were initially used to treat

Answer 51

children with epilepsy

Question 52

Do you need to know the mechanism of ketogenic diet

Answer 52

Yes

Question 53

Do you need to know about sugar tax

Answer 53

Yes bih

Question 54

Diabetes complications - Chronic hyperglycemia is a major initiator of ________ complications - Postprandial hyperglycemia is a powerful predictor of ______ complications aka ___

Answer 54

Microvascular | Macrovascular, CVD

Question 55

Do you need to know what the microvascular and macrovascular complications of diabetes are?

Answer 55

Yes

Question 56

Diabetes treatments: do you need to know - Types of therapies - Costs - Timeline

Answer 56

Yes Yes Yes

Question 57

What is the main T2DM treatment

Answer 57

Metformin

Question 58

Does metformin have a good safety profile

Answer 58

Yes

Question 59

Describe metformin mechanism of action

Answer 59

-Activates AMPK in skeletal muscle --> increased GLUT4 translocation Activates AMPK in liver --> decreased GNG Impairs absorption of glucose from the gut

Question 60

Does metformin affect insulin secretion?

Answer 60

No - rather, impacts peripheral tissues to increase insulin sensitivity

Question 61

Do you need to know about the 10 year follow up of intensive glucose control in T2D?

Answer 61

Yes

Question 62

Do you need to know about old obesity drugs and their disadvantages?

Answer 62

Yes

Question 63

For obesity, what are the 4 new drug development strategies

Answer 63

Personalised medicine Targeted therapy Monotherapies Combination therapies

Question 64

Orlistat - What is mechanism - Side effects

Answer 64

A lipase inhibitor - fat droplets pass through | Cramping, gas, diarrhea, anal leakage, oily underwear stains

Question 65

Contrave is made of what 2 drugs | Do you need to know mechanism of action, rat and human studies?

Answer 65

Buproprion and Naltrexone | Yes

Question 66

Do you need to know about liraglutide - mechansim of action, studies?

Answer 66

Yes

Question 67

What is the only effective mechanism of long term weight loss?

Answer 67

Bariatric surgery.

Question 68

What are the 3 types?

Answer 68

Gastric banding Sleeve gastrectomy Roux en Y gastric bypass

Question 69

Which is most effective and most invasive? | Which is mainly used in Aus, which in USA?

Answer 69

Roux on Y, Roux en Y Sleeve gastrectomy Roux en Y

Question 70

Gastric sleeve: -Mechanisms of action? Does it have immediate effects to improve glycemic control?

Answer 70

Stomach holds less --> increased satiation | Less ghrelin