Problem 6 - Genes vs Environment

Question 1

Obesogenic environment

Answer 1

food:
- more highly palatable & energy-dense
- easier accessible and cheaper
- bigger portions
- incentives for buying larger quantities

Exercise:

• reduced physical activity in everyday life (transportation)
• increases in range of sedentary screen based entertainments
• -> reduced activity level

higher engird-intake that energy-expenditure

Question 2

Gene-Environment Interaction

Answer 2

the more obseogenic the environment, the stronger the genetic effect on body weight
- studies found that genetic effects are moderated by environment

(found in twin studies)

Question 3

Genetics

Answer 3

genes account for 50% - 90% for differences in BMI

• genome-wide associations have (GWAS) found 97 genetic variants (SNPs)

Question 4

Behavioural Susceptibility Theory (BST)

Answer 4

Appetite mediates genetic risk of obesity

proposes that individuals who inherit a more avid appetite or lower sensitivity to satiety (‘obesity genes’)
–> they overeat in food environment

two important aspects

1. eating onset
2. eating offset
   - theory proposes that genetic risk operates through these two traits
   - they confer differential susceptibility to food environment
   - -> idea that obesity genes work through effects on appetite

Question 5

eating onset (BST)

Answer 5

responsiveness to signals to stark eating

–> ppl who are more responsive to food cues (smell, sight, taste) are more likely to eat in response to tempting opportunities

Question 6

eating offset

Answer 6

responsiveness to stop signals

–> ppl who have weaker internal signalling from their gut once they start eating or are less aware go the signals (sensitivity to satiety) are likely to carry on eating for longer once they have started

Question 7

Reward Sensitivity

Answer 7

personal risk factor

• explains individual differences in rewards motivation
• high –> more vulnerable to rewarding properties of food cues and generate approach behaviour
  youth with high sensitivity show higher intakes of palatable, energy-dense foods & sugar-sweetened beverages
• obese adults with binge eating appear to have greater responsiveness ness to food and a genotype related ti greater reward sensitivity

Question 8

Reward Deficiency Syndrom (reward sensitivity)

Answer 8

addictive substances are used as a form of medication used to boost a sluggish or hypo-functionunfg reward system and to increase hedonic capacity
(Taq1a+ allele)

Question 9

Hypersensitivity to rewards

Answer 9

contributes to increased vulnerability for overeating because of an enhanced motivation to engage in pleasurable activities
(opioid receptor gene OPRM1 in binge eating disorder patients)

Question 10

Impulsivity

Answer 10

1. failure to disinhibit inappropriate behaviour
2. heightened sensitivity to reward (without appropriate sensitivity to punishment)

–> reward-based sensitivity
(has shown to be strongly associated with overeating and weight gain)

• impulsivity also part of poor decision-making, esp. when outcome of immediate action has future consequences

Question 11

Attention Deficit/Hyperactivity Disorder ADHD

Answer 11

impulsivity * reward sensitivity converge as risk factors for obesity

• low mesolimbic dopamine availability (cause of ADHD symptoms)
• some cases of obesity may be the consequence of a food addiction38 that occurs, such as drug dependence, with greater prevalence in those with ADHD

Question 12

Environmental Factors

Answer 12

• obesigenic environment

stable behavioural phenotypes that confer risk:
- food responsiveness, reinforcing value of food,
eating in absence of hunger,
habitual consumption of high fat diets, weak satiety, disinhibition

Question 13

Genetic Factors

Answer 13

candidate gene variants presupposing to polygenic obesity generally relate to the regulation of energy intake and expenditure and include

• adrenergic receptors, uncoupling proteins, peroxisome proliferator-activated receptor (PPARG)
• proopoimelanocortin (POMC)
• melanocortin (MC4R)

Question 14

Genetic Factors

Answer 14

candidate gene variants presupposing to polygenic obesity generally relate to the regulation of energy intake and expenditure and include

• adrenergic receptors, uncoupling proteins, peroxisome proliferator-activated receptor (PPARG)
• proopoimelanocortin (POMC)
• melanocortin (MC4R)
• and fat mass and obesity associated (FTO) genes

Question 15

FTO

Candiate Gene Variants in Obesity Risk

Answer 15

• adults homozygous for the risk allele (in form of a SNP) weigh 3 kg and are more likely to be obese
• Frequency of the risk allele is estimated at ~39% in populations of European descent
• FTO gene is located on chromosome 16 + expressed mostly in brain, pancreatic islets,
  adipose tissue and adrenal glands →HPA axis
• FTO gene indicates higher risk for obesity that is conferred by differences in energy intake rather than expenditureA allele carriers:
• in children associated with lower satiety responsiveness
  + more EAH (= eating in absence of hunger), but no impact on reported activity measures
  + more consumption of energy-dense food
  ➔ Physical activity attenuates the genetic susceptibility to
  overweight and obesity conferred by the A allele of FTO

Question 16

precision medicine

Answer 16

tailoring of medical treatment to the individual characteristics of each patient & ability to classify individuals into subpopulations differing in susceptibility to particular disease , in biology or prognosis of disease or in response to specific treatment

–> seeks to maximise effectiveness by taking individual genetic variability into account

Question 17

behavioural phenotypic

Answer 17

patterns of behaviour that are distinct, are quantifiable and measurable and result from interaction of genotype with environment

• individual appetitive traits combining to make up broader eating phenotype (can help to predict response to intervention & match prevention and treatment approaches)

Question 18

Appetitive traits

Answer 18

self-regulation

Question 19

Self-Regulation

Answer 19

some (not all) infants born with capacity to self-regulate energy intake

• can self-regulate at young age (unclear why differences)
• breastfed better able regulate energy intake and lower risk of weight gain

Individual differences in satiety (caloric compensation)

• individuals with obesity showing impaired sensitivity to internal satiety cues
• satiety value of food typically assessed by consuming it as compulsory first course (preload) at peak and measuring effect in ad libitum energy intake at subsequent main course (test meal)
• poorer energy compensation ability in children associated with higher child weight status, over age, racial/ethnic minority status, having mothers who use controlling/restrictive feeding practices

Question 20

energy compensation

Answer 20

adjustments in intake in response to changes in energy density of compulsory preload –> measure of individual differences in satiety

Question 21

food-seeking appetitive traits

Answer 21

eating in absence of hunger (EAH)

relative reinforcing value of food (RRVF)

reward sensitivity

eating rate

Question 22

relative reinforcing value of food (RRVF)

Answer 22

• examines how hard individuals are willing to work to gain access to preferred food rather than appealing nonfood alternative (uses behavioural economics concept)
• sig interaction between children’s weight status, reinforcer type and schedule of reinforcement
• -> obese & overweight found food more reinforcing than nonfood & more motivate to work for food

Question 23

eating in absence of hunger (EAH)

Answer 23

• eating beyond satiation when high energy-dense snack foods are there

Question 24

eating rate

Answer 24

• rapid eating rate possible behavioural phenotype for childhood obesity
• rate of eating shown to be heritable
• emerges early in life
• may be risk factor for excess weight gain in children

Question 25

Twin studies (gene-environmental interaction)

Answer 25

• gene-envornment interplay explains much of variability in heritability of body weight
• heritability estimates higher in more obesogenic environments
• -> the more obesogenic, the greater the genetic influence on weight
• prevalence higher in families of low socioeconomic status

Question 26

externality theory (related to BST) (Schachter, 1968)

Answer 26

obese individuals have two distinct aberrations in appetite regulation leading to overeating

1. overly responsive to highly palatable food cues
2. under-responsive to internal satiety mechnism

Question 27

BST (Wardle)

Answer 27

Wardle made link between Schaters appetitive characteristic and genetic risk of obesity

• explains how this interaction (gene-environment) results in weight again
• proposing genetically determined differences in appetite as mediator
• genes set our potential for becoming obese and environment determines the outcome

Question 28

Child Eating Behaviour Questionnaire (CEBQ)

Answer 28

parent-report psychometric measure of range of children’s appetitive characteristics –> test BST in children sample

• advantage: characterising habitual eating behaviour over many meals ans situations –> caputure appetitive trait rather than state of hunger/fullness
• parent-report subjective BUT validated against objective measured eating behaviour
• comprehensive measure of all observable aspects of children’s eating behaviour hypothesised to play role in overweight or protect against it
• reposing on items on a five-point frequency scale
• good internal & external reliability, now also in babies (BEBQ) and adults (AEBQ)

Question 29

Items in the CEBQ:

responsively to food cues

Answer 29

two scales about the Schaters measures of responsibility to food cues –> predispose overweight

> food responsiveness: tendency to want to eat when prompted with palatable food 
> enjoyment of food: subjective reward experience while eating 

• higher scores = more avid appetite

Question 30

Items in the CEBQ:

Behavioural measure of responsively to internal satiety cues

Answer 30

two scales

• protect overweight
• satiety responsiveness: Childs fulness threshold
• slowness in eating: pace which child finishes meal

–> higher score = better appetitive control

Question 31

Items in the CEBQ:

Tendency to under- or overeat in response to negative emotions

Answer 31

two scales

• emotional overeating: predispose to overweight
• emotional undereating: protect against overweight> food fussiness: tendency for child to be highly selective about what to eat (protect)

Question 32

variation in appetitive traits drives weight gain

Answer 32

cross-sectional research on CEBQ:
- food responsiveness enjoyment of food –> positively related to adiposity
- satiety sensitivity & slowness in eating→negatively related to adiposity
- not simply distinguishing clinically obese from healthy-weights BUT explain
more subtle variation in weight
- BUT cannot provide insight in direction of relationship between appetite and
weight

o “Gemini” (Wardle)→large population-based prospective birth cohort of 2402 infant
twin pairs to examine genetic and environmental influence
▪ hypothesis: variation in appetite at 3 months driving early weight gain from 3
to 15 months, not other way around (weight variation predicting appetite
change) → SUPPORT

Question 33

Appetitive traits mediate genetic influence on weight

Answer 33

BEBQ in in Gemini (study):
- relative contribution of genetic and environmental influence to variation in appetitive characteristics during earliest period of life (still milk-fed)

heritability substantially for 
 > enjoyment of food (53%)
 > food responsiveness (59%)
 > satiety responsiveness (59%) 
 > slowness in eating (84%)

–> very early infants vary considerably in appetite –> both associated with weight gain and genetically based

• approx. 1/3 genetic influences underlying 3-month weight are same as those underlying appetite
• -> supports hypothesis that genes influence weight partly through effects on appetite (moderator?)

Question 34

FTO (twin studies)

Answer 34

investigated in twin studies

-10-year old children who carried at least one copy of lower risk
variant of FTO (TT or AT) were sign. more satiety sensitive
- compared with those with two copies of higher risk version (AA)
- FTO influences body weight via impacting satiety sensitivity

Question 35

adult studies

Answer 35

questionnaire measures of uncontrolled eating and emotional
eating associated with genetic risk of obesity

• these appetitive traits mediated part of association between genetic risk
  score and adiposity

Question 36

behavioural expressions of appetitive traits and weight gain

Answer 36

HOW genetically determined appetitive traits lead to weight gain in response to obseogenic environment.

Gemini study:
- greater reponsiveness to food cues and blunted satiety sensitivity characterised by distinctive
everyday patterns of excessive intake in young children
- 2 possible patterns of overeating

1. eating more frequently throughout day
   > more food responsive ch. ate more often throughout day but not larger amount each time
   > highly responsive to food cues = eat more often in food environment
2. consuming larger average meal sizes
   > children with impaired satiety sensitivity consumed larger average meal sizes each time they ate, but not eating more frequently
   > weaker satiety signals = overeat in response to larger portion sized because take longer to feel full