Obesity Flashcards
Do you need to know what the BMI classifications are
Yes
Do you need to know what risk factors for obesity are?
Yes
Do you need to now the prevalence of obesity - both globally and locally?
Yes
Is there a genetic predisposition to obesity?
Does obesity tend to be monogenic or polygenic?
Polygenic
4 genetic causes of obesity
Prader Willi syndrome
Leptin deficiency
Leptin receptor deficiency
FTO gene
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?
YEs
YEs
Yes
Increased ghrelin levels
Leptin deficiency
- Describe how it contributes to obesity
- Can it be cured with leptin replacement?
- Do you need to know rat studies?
Mutation in ob gene –> leptin not produced. Lack of satiety signal –> constantly hungry and eating –> obesity
Yes
Yes
Leptin receptor mutations
- Can it be cured with leptin replacement?
- Do you need to know rat studeis?
No
Yes
Sometimes, are environmental factors needed to unmask genetic predisposition to obesity?
Yes
Can set point be re established in children and adults? Implication?
Do you need to know study?
Only children - can reestablish weight trajectory.
Yes
Do you need to know animal studies?
Yes
What would you expect to happen when you increase energy expenditure vs what actually happens, and why?
Lose weight
Weight maintained - as compensatory increase in food intake
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?
Yes
Yes
Yes
Do you need to know
- Various brain nuclei involved in appetite
- Dual centre hypothesis - VMH and LH
- Is everything else in the visual diagram?
Yes
Yes
Yes
Do you need to know the following aspects about metabolic syndrome:
-Definition/diagnosis
Risk factors
Consequences
Yes
Is BMI assocaited with increased chronic illness risk and mortality
Yes
Do you need to know the following about T2D:
- Prevalence
- Heritability
- Diagnosis
Yes
Do you need to know about insulin resistance mechanisms in the liver, skeletal muscle and adipose tissue?
Yes
Where does glucose uptake primarily occur, and what is the primary site of insulin resistance?
Skeletal muscle
Describe the two phases of type 2 diabetes pathogensis
Insulin resistance occurs.
Initially, beta cells secrete more insulin to keep BGLs stable. But then beta cells undergo failure –> BGLs soar
What 4 mechanisms contribute to insulin resistance?
Do you need to know these in detail?
Lipotoxicity
Inflammation
Altered endocrine signals
Mitochondrial dysfunction
Yes
Do you need to know the classifications of physical activity intensity, in terms of metabolic equivalents of tasks?
Yes
What is an active couch potato
People who are highly active byt highly sedentary
What fraction of people worldwide are physically inactive? Are males or females more inactive?
1/4, generally females.
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?
Yes
Yes
Do you need to know the health consequences of sedentary behaviour?
Yes
What combination of activity vs sedentary behaviour results in highest risk of mortality?
Low activity, high sedentary
Has COVID increased sedentary time and decreased physical activity time?
Yes
What are the 4 mechanisms through which sedentary behaviour increases chronic illness risk? Do you need to know these?
Increased blood glucose
Increased blood pressure
Impaired vascular function
REduced cerebral blood flow
Yes
Do you need to know the 3 studies?
Yes
Do you need to know the guidelines
Yes
what are the 3 components of energy expenditure?
Obligatory energy expenditure
Physical activity
Adaptive thermogenesis
Obligatory energy expenditure is aka
resting energy expenditure
basal metabolic rate
Is BMR correlated to lean (fat free) body mass?
Do females have lower BMR than males?
Does BMR decrease over the lifespan
Yes Yes Yes
Is weight change in response to exercise genetically determined? Do you need to know the studies?
Yes
Do you need to know the exercise requirements for clinically significant weight loss?
Yes
Do you need to know the benefits of exercise beyond weight loss?
Yes
What is non exercise adaptive thermogenesis?
Energy used during physical activities that don’t involve volitional exercise
What are the 2 sites of adaptive thermogenesis?
Brown adipose tissue
Skeletal muscle
Brown adipose tussue: describe stimulus and response of adaptive thermogenesis
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.
BAT: do you need to know studies?
Yes
In skeletal muscle, describe the types of UCP proteins
Mainly UCP3, some UCP2
Is UCP3 as effective as UCP2, and if not what counteracts this?
No, high skeletal muscle mass
In addition to UCPs, what is the other pathway that contributes to thermogenesis in muscle? Do you need to know mechanism?
Calcium cycling, yes
Do you need to know the interindividual variation in posture allocation - role in human obesity study?
Yes
Do you need to mnow the location of the adipocyte types, and changes in location over the lifespan
Yes
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
Yes Yes Yes
After weight loss, what happens to
- total energy expenditure
- hunger signals
- satiety signals
- Do you need to know the studies?
Total energy expenditure decreases
Satiety signals decrease
Hunger signals increase
Do you need to understand weight cycling? What happens to weight over time?
Yes, keeps increasing
Do you need to know the mouse yoyo dieting study?
Yes
Ketogenic diets were initially used to treat
children with epilepsy
Do you need to know the mechanism of ketogenic diet
Yes
Do you need to know about sugar tax
Yes bih
Diabetes complications
- Chronic hyperglycemia is a major initiator of ________ complications
- Postprandial hyperglycemia is a powerful predictor of ______ complications aka ___
Microvascular
Macrovascular, CVD
Do you need to know what the microvascular and macrovascular complications of diabetes are?
Yes
Diabetes treatments: do you need to know
- Types of therapies
- Costs
- Timeline
Yes Yes Yes
What is the main T2DM treatment
Metformin
Does metformin have a good safety profile
Yes
Describe metformin mechanism of action
-Activates AMPK in skeletal muscle –> increased GLUT4 translocation
Activates AMPK in liver –> decreased GNG
Impairs absorption of glucose from the gut
Does metformin affect insulin secretion?
No - rather, impacts peripheral tissues to increase insulin sensitivity
Do you need to know about the 10 year follow up of intensive glucose control in T2D?
Yes
Do you need to know about old obesity drugs and their disadvantages?
Yes
For obesity, what are the 4 new drug development strategies
Personalised medicine
Targeted therapy
Monotherapies
Combination therapies
Orlistat
- What is mechanism
- Side effects
A lipase inhibitor - fat droplets pass through
Cramping, gas, diarrhea, anal leakage, oily underwear stains
Contrave is made of what 2 drugs
Do you need to know mechanism of action, rat and human studies?
Buproprion and Naltrexone
Yes
Do you need to know about liraglutide - mechansim of action, studies?
Yes
What is the only effective mechanism of long term weight loss?
Bariatric surgery.
What are the 3 types?
Gastric banding
Sleeve gastrectomy
Roux en Y gastric bypass
Which is most effective and most invasive?
Which is mainly used in Aus, which in USA?
Roux on Y, Roux en Y
Sleeve gastrectomy
Roux en Y
Gastric sleeve:
-Mechanisms of action?
Does it have immediate effects to improve glycemic control?
Stomach holds less –> increased satiation
Less ghrelin
