Physiology of Appetite and Weight

Question 1

Obesity can be viewed in two ways:

1. As a medical problem
   
   • aetiology - … and …
2. As a personal failure
   
   • lack of …

Answer 1

1. As a medical problem
   
   • aetiology - genetic and environmental
2. As a problem failing
   
   • lack of self-discipline

Question 2

Obesity definition - Prof Steve O’Rahilly:

• ’ a … hereditary disorder heavily influenced by the … ‘

Answer 2

• ’ a neurobehavioural hereditary disorder heavily influenced by the environment ‘

Question 3

Homeostasis - precise matching of energy intake and energy expenditure:

• average decade of adult life - we consume around how many calories?
• tendency towards a slight average weight ….

Answer 3

• average decade of adult life - we consume around how many calories? - 10 million
• tendency towards a slight average weight gain

Question 4

Measurements - weight

• Body mass index (BMI) - measured in …
• waist …
• skin-… thickness
• … impedance analysis
• ethnicity specific …

Answer 4

• Body mass index (BMI) - kg/m2
• waist circumference
• skin-fold thickness
• bioelectrical impedance analysis
• ethnicity specific cut-offs

Question 5

Body mass index (BMI) ranges

• Underweight = ?
• Normal = ?
• Overweight = ?
• Obese = ?
• Morbid Obesity = ?

Answer 5

• Underweight = <18.5
• Normal = 18.5-24.9
• Overweight = 25-29.9
• Obese = 30-39.9
• Morbid Obesity = > (And including) 40

Question 6

What trend is this showing? (prevalence increasing)

Answer 6

obesity trends among US adults

also in europe (shown below)

Question 7

Medical Problems of Obesity:

• … syndrome / type … diabetes
• … disease
• … disease
• … disease
• Cancer
• Reproductive …
• … problems
• … health

Answer 7

• Metabolic syndrome / type 2 diabetes
• CVS disease
• Respiratory disease
• Liver disease
• Cancer
• Reproductive dysfunction
• Joint problems
• Mental health

Question 8

Once you become significantly or morbidly obese, what happens to co-morbidities?

Answer 8

Will have more than 1 associated with your obesity

Some patients have 3 or more co-morbidities - this % rises as BMI rises

(>60 BMI = 90% have 3 or more co-morbidities)

Question 9

Some of the health risks start to go up in the … category of BMI range

Answer 9

Some of the health risks start to go up in the overweight category of BMI range (25-30)

Question 10

What is metabolic syndrome?

• what are some examples of conditions involved?
• what is the underlying pathophysiological mechanism?

Answer 10

A constellation of closely associated cardiovascular risk factors

• e.g. visceral obesity, dsylipidaemia, hyperglycaemia, hypertension
• underlying mechanism - insulin resistance

Question 11

Obesity - Insulin resistance and the metabolic syndrome

• BMI vs body fat distribution (central vs peripheral)
• Metabolic syndrome is associated with 1) … fat distribution and 2) body mass index of over …

Answer 11

• BMI vs body fat distribution (central vs peripheral)
• Metabolic syndrome is associated with - central (visceral fat) and body mass index >30

Question 12

Obesity - pathophysiology of insulin resistance

• One idea - release of free … …
  
  • leading to … of visceral fat
  • -> gluconeogenesis
  • -> dyslipidaemia
• other idea - release of pro-inflammatory …
  
  • TNF-a, IL-6 (from overload white adipose tissue)
  • causing insulin resistance
  • reduced expression of GLUT 4
  • decreased … kinase activity of insulin receptor

Answer 12

• One idea - release of free fatty acids (non-esterified fatty acids)
  
  • lipolysis of visceral fat
  • gluconeogenesis
  • dyslipidaemia
• other idea - release of pro-inflammatory cytokines
  
  • TNF-a, IL-6 (from overload white adipose tissue)
  • causing insulin resistance
  • reduced expression of GLUT 4
  • decreased tyrosine kinase activity of insulin receptor

Question 13

fat is a very … tissue - it produces …

Answer 13

fat is a very active tissue and it produces adipocytokines

Question 14

Type 2 diabetes

• Risk is determined by 4 factors. What are they?
• Targets: does it target rich or poor?

Answer 14

• Age
• Obesity
• Family Hx
• Ethnicity
• Targets - rich in poor countries, poor in rich countries (source of socioeconomic inequality in health)

Question 15

Why is the prevalence of Type 2 Diabetes rising?

Answer 15

• Increasing age of population
• Increasing obesity levels
  
  • T2 DM younger
• Increased detection/diagnosis - 50% cases picked up on routine examination
• Increased survival with T2 DM

Question 16

Cardiovascular disease - associated with obesity

• ‘… syndrome’ PLUS
  
  • increased blood … and blood …
  • increased vascular …
  • increased …tension
  • increased left ventricular …
  • increased … artery disease
  • increased risk of …

Answer 16

• ‘Metabolic syndrome’ PLUS
  
  • increased blood volume and blood viscosity
  • increased vascular resistance
  • increased hypertension
  • increased left ventricular hypertrophy
  • increased coronary artery disease
  • increased risk of stroke

Question 17

Respiratory System - associated with obesity

• Obstructive … …
• Hyp../hyper…
• Pulmonary … - cause of … heart failure
• Accidents - daytime …

Answer 17

• Obstructive sleep apnoea
• Hypoxia/hypercapnia
• Pulmonary hypertension - right heart failure
• Accidents - daytime somnolence

Question 18

GI/liver - associated with obesity

• NAFLD - what does this stand for?
  
  • may be called MAFLD
  • …% of obese people have NAFLD
• 1:5 progress to NASH - what does this stand for?
• 1:5 progress to … and chronic liver disease
• Can also have …stones
• Reflux

Answer 18

• _​_Non-alcoholic fatty liver disease (NAFLD)
  
  • ‘Metabolic-associated fatty liver disease’
  • 90% of obese people have NAFLD
• 1:5 progress to non-alcoholic steatohepatitis (NASH)
• 1:5 progress to cirrhosis and chronic liver disease
• Gallstones
• Reflux

Question 19

Obesity and cancer

• Is obesity or smoking the most important cancer risk factor?
• What types of cancer are linked to obesity? (7)
• Mechanisms include … (5)

Answer 19

• Is obesity or smoking the most important cancer risk factor? - obesity has overtaken smoking
  
  • What types of cancer are linked to obesity? (7)
    
    • breast
    • endometrial
    • oesophagus
    • colon
    • gall bladder
    • renal
    • thyroid
• Mechanisms include … (5)
  
  • increased insulin
  • increased free IGF-1
  • Increased oestrogen
  • adipo-cytokines
  • reflux

Question 20

Reproductive system and Obesity

• In women - PCOS is strongly associated with obesity - what does this stand for? what does it cause? (6 things)
• In men - male hypo..
• adverse … outcomes

Answer 20

• In women - PCOS is strongly associated with obesity - what does this stand for? Polycystic ovarian syndrome what does it cause? (6 things)
  
  • oligomenorrhoea, hirsutism, acne, subfertility, endometrial hyperplasia, insulin resistance
• male hypogonadism
• adverse pregnancy outcomes

Question 21

Effect of weight loss on testosterone

The bigger weight loss, the … the testerone

Answer 21

higher testosterone - levels increase

Question 22

Joints and obesity

• osteo…
• also g…

Answer 22

• osteoarthritis
• gout

Question 23

Mental Health and Obesity

• obesity is associated with:
  
  • …
  • … disorders
  • …

Answer 23

• depression
• eating disorders
• dementia

Question 24

Covid 19 and Obesity

• impact of obesity on C19
  
  • increased prevalence
  • increase risk of …
  • increased risk of … admission
  • increased …
  • ‘…-response’ with BMI
    
    • independent of…
    • related to increased … fat

Answer 24

• impact of obesity on C19
  
  • increased prevalence
  • increase risk of hospitalisation
  • increased risk of ICU admission
  • increased mortality
  • ‘dose-response’ with BMI
    
    • independent of co-morbities
    • related to increased visceral fat

Question 25

Covid 19 and Impact of lockdown on Obesity

• increased … of food
• increased …-induced eating
• decreased … health
• reduced …
• less access to …-management services

Answer 25

• increased stockpiling of food
• increased stress-induced eating
• decreased mental health
• reduced exercise
• less access to weight-management services

Question 27

Aetiology of obesity

• … factors
• … factors
• programming
• gut …

Answer 27

• genetic factors
• environmental factors
• programming
• gut microbiome

Question 28

Genetics - obesity

• Rare - Obesity-associated syndromes
  
  • …-willi
  • …-biedl
• Common - polygenic
  
  • … genes
  • heritability of weight - similar to heritability of …

Answer 28

• Rare - Obesity-associated syndromes
  
  • prader-willi
  • bardet-biedl
• Common - polygenic
  
  • susceptibility genes
  • heritability of weight - similar to heritability of height

Question 29

Other causes of obesity (endocrine) include… (2)

Answer 29

• hypothyroidism
• Cushing’s syndrome

Question 30

Environment and Obesity

• Diet
  
  • which is high in … and …
  • ‘Coca-colanisation’ of developing world
  • …-… factors
• Physical activity
  
  • …-…% of total energy expenditure
  • obesity prevalence related to proxy measures of physical activity - … ownership, … viewing
  • …-… factors

Answer 30

• Diet
  
  • high fat and sugar
  • ‘Coca-colanisation’ of developing world
  • socio-economic factors
• Physical activity
  
  • 20-50% of total energy expenditure
  • obesity prevalence related to proxy measures of physical activity - car ownership, TV viewing
  • Socio-economic factors

Question 31

Fetal Programming - Obesity

• ‘programming’: stimuli/insults at critical periods have persistant biological effects
• ‘…’ in utero
  
  • undernutrition? trace elements? other?
  • crudely represented by birth …
• mechanism - epigenetic modification of gene expression
  
  • example?

Answer 31

• ‘programming’: stimuli/insults at critical periods have persistant biological effects
• ‘stressors’ in utero
  
  • undernutrition? trace elements? other?
  • crudely represented by birth weight
• mechanism - epigenetic modification of gene expression
  
  • example - low birth weight - programmed adrenal axis overactivity in adulthood
  • causal factor for metabolic syndrome
  • increased vulnerability to coronary heart disease

Question 32

Life course model

• factors operating at every stage of life affect health outcomes later in life
• ‘pathway of risk’ between events and health outcomes
• ‘worst outcome’ associated with:
  
  • low … ..
  • excessive … gain in infancy/childhood
  • adult …

Answer 32

• factors operating at every stage of life affect health outcomes later in life
• ‘pathway of risk’ between events and health outcomes
• ‘worst outcome’ associated with:
  
  • low birth weight
  • excessive weight gain in infancy/childhood
  • adult obesity

Question 33

Gut Microbiome

• Gut microbiome - lots of cells in colon
• More genes than in human genome
• Integral to host …
• Influenced by diet
  
  • high in .., high … etc
• Influences disease risk
  
  • such as … and … diabetes

Answer 33

• Gut microbiome - lots of cells in colon
• More genes than in human genome
• Integral to host homeostasis
• Influenced by diet
  
  • high in fat, high fibre etc
• Influences disease risk
  
  • obesity, T2 DM

Question 34

Gut Microbiome - Obesity and T2 Diabetes vs Normal

• There are differences in gut …
  
  • can be induced by diet e.g. high fat diet
• transplantation of faecal material alters … sensitivity

Answer 34

• There are differences in gut bacteria
  
  • can be induced by diet e.g. high fat diet
• transplantation of faecal material alters insulin sensitivity

Question 35

Regulation of Appetite & Weight

• Slow-acting hormones that regulate body weight - what are 2 examples?
• these signal % of … to hypothalamus
  
  • decreased …
  • increased … expenditure
• rapid-acting peptides that regulate meal sizes - released from GI tract
  
  • PYY - does it inhibit eating?
  • Ghrelin - does it inhibit eating?
  • CCK - does it inhibit eating?
    
    • (act via …)

Answer 35

• Slow-acting hormones that regulate body weight
  
  • leptin
  • insulin
• signal %body fat to hypothalamus
  
  • leading to decreased food intake
  • increased energy expenditure
• rapid-acting peptides that regulate meal sizes - released from GI tract
  
  • PYY - does it inhibit eating? - yes (up to 12 hours)
  • Ghrelin - does it inhibit eating? - no - stimulates it
  • CCK - does it inhibit eating? - yes
    
    • (act via hypothalamus)

Question 36

Hypothalamus - Arcuate nucleus

• 2 groups of neurons - ‘… neurons’ and ‘… neurons’
• Different peptides affect … behaviour and expenditure

Answer 36

• ‘Acceletor neurons’ and ‘brake neurons’
• Different peptides affect eating behaviour and expenditure

Question 37

Leptin and appetite/weight

• ob/ob mouse on left - did it have leptin?
• db/db mouse - plenty of leptin but …
• ob gene product =

Answer 37

• No - leptin deficient
• db/db mouse - plenty of leptin but mutation of leptin receptor
• ob gene product = lectin

Question 38

Leptin treatment … obesity in ob/ob mouse

Answer 38

Leptin treatment reduces obesity in ob/ob mouse

Question 39

Leptin (Humans)

• Leptin is more of a ‘… signal’
• Has a permissive effect on …/…
• In obese humans - very rare examples of people who are …
  
  • leptin …
  • … of leptin receptor
• Usually
  
  • increased leptin with … fat
  • in obesity - develop some form of leptin …
  • Also decreased … leptin transport with … fat

Answer 39

• Leptin is more of a ‘Starvation signal’
• Has a permissive effect on puberty/reproduction
• In obese humans - very rare examples of people who are …
  
  • leptin deficient
  • mutation of leptin receptor
• Usually:
  
  • increased leptin with increased fat
  • in obesity - develop some form of leptin resistance
  • Also decreased CNS leptin transport with increased fat

Question 40

Talking with patients - Obesity

• Language matters
  
  • obesity is a medical definition but can be a problematic term for patients - why?
• seek … to discuss weight
• preferred terms to consider - what are these?

Answer 40

• Language matters
  
  • obesity is a medical definition but can be a problematic term for patients - negative connotations and stigmatising
• seek permission to discuss weight
• preferred terms to consider - what are these?
  
  • Overweight
  • Carrying too much weight

Question 41

Lifestyle modifications - Obesity: Diet

• Deficiency of … - … kcal energy deficiency
• Low energy density
  
  • decrease … fats and …
  • increase … and …
• decreased … sizes and snacking
• structured meals / meal … may help promote greater weight loss

Answer 41

• Diet
  
  • Deficiency of 500-1000 kcal energy deficiency
• Low energy density
  
  • decrease saturated fats and sugar
  • increase fruit and beg
• decreased portion sizes and snacking
• structured meals / meal replacements may help promote greater weight loss

Question 42

Lifestyle modifications - Obesity: Physical Activity

• Exercise … days a week
  
  • … mins moderate-high intensity OR
  • … mins low intensity
• taking … steps / day
  
  • increase in … step increments
• regardless of weight / weight loss, exercise increases health

Answer 42

• Exercise 7 days a week
  
  • 30 mins moderate-high intensity OR
  • 60 mins low intensity
• taking 10,000 steps / day
  
  • increase in 500 step increments
• regardless of weight / weight loss, exercise increases health

Question 43

Very Low Calorie Diet and T2 Diabetes

• Principle:
  
  • Primary care programme
  • Patients with T2 DM diagnosis <6 years prior
  • VLDC (830 kcal/day) for how long?
    
    • initially, total diet replacement with formulae
    • then stopped food reintroduction … - … weeks
    • long-term maintenance with structured support
• Outcomes:
  
  • 12 month outcomes
  • …% of participants achieved 15kg loss or more
  • …% induced remission of T2DM
    
    • Normal HbA1c off all medication for 2 months
  • >10kg weight loss -…% remission

Answer 43

• Principle:
  
  • Primary care programme
  • Patients with T2 DM diagnosis <6 years prior
  • VLDC (830 kcal/day) for 3-5 months
    
    • initially, total diet replacement with formulae
    • then stopped food reintroduction 2-8 weeks
    • long-term maintenance with structured support
• Outcomes:
  
  • 12 month outcomes
  • 24% of participants achieved 15kg loss or more
  • 46% induced remission of T2DM
    
    • Normal HbA1c off all medication for 2 months
  • >10kg weight loss - 73% remission

Question 44

Lifestyle modification - Obesity and weight loss

• Usual targets
  
  • …% weight loss
  • …-… lb per week
  • some evidence that ambitious goals promote … weight loss
• problems
  
  • most patients can achieve 5-10% weight loss in a year
  • ‘yo-yo’ dieting / regaining weight lost
  • obesogenic environment
  • weight loss results in increased …, decreased …, decreased … rate
• best hope :
  
  • sustainable lifestyle changes
  • diet combined with exercise / physical activity
  • ongoing management is required to maintain weight loss

Answer 44

• Usual targets
  
  • 10% weight loss
  • 1-2 lb (0.5-1kg) per week
  • some evidence that ambitious goals promote more weight loss
• problems
  
  • most patients can achieve 5-10% weight loss in a year
  • ‘yo-yo’ dieting / regaining weight lost
  • obesogenic environment
  • weight loss results in increased hunger, decreased satiety, decreased metabolic rate
• best hope :
  
  • sustainable lifestyle changes
  • diet combined with exercise / physical activity
  • ongoing management is required to maintain weight loss

Question 45

Pharmacological Therapy for Obesity

• only 1 currently licensed drug - what is this?

Answer 45

• orlistat

Question 46

Orlistat

• Mechanism
  
  • Binds and inhibits … in the lumen of the gut
  • prevents the … of dietary fat into absorbable free fatty acids/ glycerol
  • excrete - …rd dietary fat
• Adverse effects include:
  
  • flatulence, oily … leakage, diarrhoea
  • decreased absorption of … soluble vitamins
    
    • ADEK
      
      • Supplement

Answer 46

• Mechanism
  
  • Binds and inhibits lipases in the lumen of the gut
  • prevents the hydrolysis of dietary fat into absorbable free fatty acids/ glycerol
  • excrete - 1/3rd dietary fat
• Adverse effects include:
  
  • flatulence, oily faecal leakage, diarrhoea
  • decreased absorption of fat soluble vitamins
    
    • ADEK
    • Supplement

Question 47

Metformin

• The best 1st line agent for … patients with … diabetes
  
  • ​used in diabetes prevention trials but not licensed for this use
• recommended by NICE for prevention of … in adults at … risk

Answer 47

• The best 1st line agent for over-weight/obese patients with Type 2 diabetes
  
  • ​used in diabetes prevention trials but not licensed for this use
• recommended by NICE for prevention of Type 2 DM in adults at high risk

Question 48

Pharmacological therapy for obesity

• Problems
  
  • can only increase by …-… fold the proportion of patients who achieve 5% weight loss in a year
  • weight … after treatment stopped
• The Future:
  
  • all identified … are potential therapeutic targets / options
    
    • … in combination most likely way forwards

Answer 48

• Problems
  
  • can only increase by 3-4 fold the proportion of patients who achieve 5% weight loss in a year
  • weight re-gain after treatment stopped
• the future:
  
  • all identified gut peptides / neuropeptides / their receptors are potential therapeutic targets / options
    
    • gut hormones in combination most likely way forwards

Question 49

Surgical Treatment - Obesity

• 2 options - what are they?

Answer 49

• 2 options:

1. Laparoscopic adjustable banding
2. Roux-en Y gastric bypass

Question 50

Laparoscopic adjustable banding

• Restrictive or not?
• Inject/withdraw … to adjust … of the band

Answer 50

• Restrictive or not - yes
• Inject/withdraw saline to adjust diameter of the band

Question 51

Roux-en Y gastric bypass

• It is both … and ….
• Alterations in gut … and … acid flow contribute to weight loss
• Complications include:
  
  • … deficiencies such as …
  • … syndrome
    
    • GI and vasomotor symptoms
  • Post-prandial …

Answer 51

• Restrictive and malabsorptive
• Alterations in gut hormones and bile acid flow contribute to weight loss
• Complications include:
  
  • Micronutrient deficiencies such as iron, B12, folate, calcium, vitamin D - important to supplement
  • Dumping syndrome
    
    • GI and vasomotor symptoms
  • Post-prandial hypoglycaemia

Question 52

Roux-en Y gastric bypass - rat experiment

• Plasma from operated rats to sham-operated rats - what was the effect?

Answer 52

• ate 1/3rd less

Question 53

People who have had Roux-en Y gastric bypass surgery claim to feel …

Answer 53

more full - increased satiety

Question 54

Surgical treatment for Obesity

• Advantages include:
  
  • weight loss of …%
  • resolve or improve …
    
    • brings …-savings
• Disadvantages
  
  • Perioperative mortality/morbidity
    
    • depends on procedure and experience of surgeon
  • complications
    
    • requires … term follow up
  • some weight …
    
    • patients will still be obese
  • expense
    
    • though cost effective by … - … years, depending on co-morbidities and weight

Answer 54

• Advantages include:
  
  • weight loss of 25-30%
  • resolve or improve co-morbitities
    
    • brings cost-savings
• Disadvantages
  
  • Perioperative mortality/morbidity
    
    • depends on procedure and experience of surgeon
  • complications
    
    • requires long term follow up
  • some weight re-gain
    
    • patients will still be obese
  • expense
    
    • though cost effective by 2-5 years, depending on co-morbidities and weight

Question 55

UK position bariatric surgery - NICE guidelines

• NICE 2005
  
  • referal only when?
  • BMI must be > … or > … with co-morbid conditions
  • First line treatment if BMI is > …
• NICE 2014
  
  • Recent onset of … means you can:
    
    • Expedite surgery if BMI is > ….
    • Consider surgery if BMI > …

Answer 55

• NICE 2005
  
  • referal only if failure of other options
  • BMI must be > 40 or > 35 with co-morbid conditions
  • First line treatment if BMI is > 50
• NICE 2014
  
  • Recent onset of T2DM
    
    • Expedite surgery if BMI is > 35
    • Consider surgery if BMI > 30

Question 56

UK position bariatric surgery - NHS guidelines

• NHS England 2013:
  
  • As per NICE but…
    
    • must have been obese for how long?
    • must engage with what?

Answer 56

• must have been obese for at least 5 years
• must engage with non-surgical weight-loss programme for 12-24 months first

Question 57

Public Health/Societal - Obesity

• Schools - whats important?
• Urban design to encourage …
• Marketing/Media/Social media
  
  • food …, food …

Answer 57

• Schools - PE, lunches, vending machines
• Urban design - encouraging walking and cycling
• Marketing/Media/Social media
  
  • food labelling, food adverts

Question 58

• The combination of hypertension, dyslipidemia, insulin resistance, hyperinsulinemia, glucose intolerance, and obesity, particularly central obesity, has been termed the “…. syndrome.”
• It has been proposed that this syndrome is a powerful determinant of … and … disease.

Answer 58

• The combination of hypertension, dyslipidemia, insulin resistance, hyperinsulinemia, glucose intolerance, and obesity, particularly central obesity, has been termed the “metabolic syndrome.”
• It has been proposed that this syndrome is a powerful determinant of diabetes and cardiovascular disease.