Lecture 20 - Eating Behavior Flashcards
Energy balance and weight maintenance
Homeostasis: maintenance of a steady state of an organism by physiological or behavioural feedback control mechanisms
Feeding behaviour is governed by homeostasis
body’s need to maintain an optimal energy “set point”
Signals from the gastrointestinal tract and adipose tissue responsible for this process
There are also hedonic pathways which have a role
The interoceptive system sends inputs via parasympathetic relays to the CNS
These inputs contain information about thermal, chemical, metabolic and hormonal changes (from skin, muscle, joints, etc.)
Important part: the enteroendocrine system
Energy balance is regulated by a complex system
Orexigenic peptides: increase motivation to eat
e.g. ghrelin, NPY, AgRP, MCH, Orexin A, Orexin B, galanin
Anorexigenic peptides: decrease motivation to eat
e.g. leptin, insulin, alpha-MSH, CRH, TRH, CART, POMC, GL-P1
Ghrelin
Discovered in 1996: still new-ish by the standards of science
A peptide hormone produced by the stomach cells; it is thought to increase feelings of hunger.
Also an orexigenic hormone (stimulating appetite)
May have evolved as a response to the feast or famine conditions of early humans.
Not as relevant in situations when food is abundant
It is inhibited when the stomach is stretched and designed for situations of feast/famine
Ghrelin System
Secreted from empty stomach
- Stimulates food intake
- Release stopped when -stomach stretched
Produced in the arcuate nucleus of hypothalamus
- Acts in dopaminergic centers to increase reward behaviour
- GH will take energy from good and build the body with it
- Stimulates secretion of growth hormone
Activates mesolimbic dopamine
Increases drive to consume food
Ghrelin and feeding behaviour
Systematic injections of ghrelin stimulate food intake and increase body mass in rats.
Increased hyperphagia, weight gain and adiposity occur after continuous systematic ghrelin administration at low doses
Ghrelin important in food intake
Higher levels linked to increased consumption
Blood concentrations of ghrelin peak around the time of meal onset
In humans increase nearly twofold immediately before each meal
Fall within one hour after eating
Ghrelin levels show a diurnal rhythm that is exactly in opposite phase with that of leptin – rising and falling at the opposite times during the day
This rise and fall supports the hypothesis that ghrelin plays an important role in meal initiation in humans.
Prader Willi Syndrome
Genetic disorder with mild growth retardation
Hyperphagia and obesity common, even if only bland food is available they will still eat
Elevated levels of plasma ghrelin typically observed
Missing methylation on ghrelin promoter region - excess ghrelin
Dysregulation of many hormone systems
-Insufficient growth hormone - low muscle, high fat
Incomplete sexual development
-Hypocortisolemia (underactive adrenal cortex)
Inactivity in many hormonal systems
Leptin
Leptos: “thin”
Adipokine Hormone - produced by adipose tissue
Adipocytes not just storehouses, endocrine glands too!
Levels are higher in obese people and after meals
Lower in thinner people and during fasting periods
Actions of leptin
Leptin levels are proportional to body fat and fluctuate in opposition to Ghrelin
Active transport mechanism brings leptin across BBB
NB - Ghrelin is produced in the arcuate nucleus, leptin must actively cross the BBB to get into the brain and exert an effect
Binds to receptors in hypothalamus to inhibit eating and send satiety signals
High while fat is being stored, fall when fat metabolized
High levels of leptin cause long-term satiety
Rodent Studies
- Mutations in mice in genes coding for leptin (“ob”) or leptin receptors “db”
- Leptin treatment of ob/ob mice caused significant weight loss
- Leptin critical for reducing excessive weight
Leptin was found by looking at obese mice and seeing how they differed from normal ones
ob gene = obese gene
If you have no receptor for leptin, you have the same issue
Leptin treatment can rectify obesity
Mutation of both leptin and leptin receptor genes found in humans, though very rare
Heterozygous means moderate obesity
The ob(lep) gene is found on chromosome 7
Can be treated with daily leptin injections
People with this mutation get thinner. They are still fat but not in the top 1% anymore
Pancreatic Hormones Regulate Glucose
Insulin is released immediately following a meal.
Glucose moves from the blood to other tissues.
Excess glucose is stored as glycogen, then as fat
As blood glucose levels drop, glucagon converts glycogen back into glucose
Insulin and Leptin linked: satiety hormones
(1) Insulin stores fat
(2) Leptin says we have enough nutrients stored
Fat storage vs. reducing fat stores
Opposite effect to achieve same ends
Energy balance is regulated by a complex system
Orexigenic peptides: increase motivation to eat
e.g. ghrelin, NPY, AgRP, MCH, Orexin A, Orexin B, galanin
Anorexigenic peptides: decrease motivation to eat
e.g. leptin, insulin, alpha-MSH, CRH TRH, CART, POMC, GL-P1
IDEAL WORLD ENERGY HOMEOSTASIS
When you eat ghrelin decreases and insulin increases
- Reduced hunger and absorption of sugar to maintain blood glucose
- Leptin increases with storage, reducing overall appetite, causing body to use stores
THIS DOES NOT HAPPEN!
Hedonic foods: throwing off a fine balance
Signals from outside the body (availability of food options) can alter hormonal processes
Hedonic foods are high in fat and sugar
High caloric density
Intrinsically motivating - act on the dopamine pathway of the brain to increase their incentive salience (drive to get and consume)
What’s gone wrong with our energy homeostasis
How do current eating patterns dysregulate this process?
Highly palatable food readily available
Often fastest and cheapest options
Obese people greater responsivity to food cues
Ghrelin – reduced in obesity
Reduced growth hormone so increased adipose storage….
Stomach size
Leptin does not readily cross blood brain barrier
Heightened levels of blood leptin are not absorbed into the CNS
Aging may also contribute to leptin resistance
Resistance to satiety hormones
CHRONIC HIGH LEVELS CAN DECRESE THE EFFECTIVNESS OF INSULIN AND LEPTIN
Insulin resistance
How do current eating patterns dysregulate this process?
Hedonistic driven eating = chronically high blood glucose
Insulin released in response to eating/blood sugar
Chronic high insulin reduces receptors
Insulin resistance means no effect of this satiety hormone
Major factor in type 2 diabetes
Insulin resistance closely linked to leptin resistance
Satiety hormones both have little effect
Experiment in overfeeding rats
Rats: can control all food intake and limit activity
-Eliminate all confounding variables
Compare rats getting healthy and high fat food
Add pair-fed to assess role of control over food consumption
(Healthy food by in the same number of kcals as non-healthy food)
Administer insulin + glucose and leptin
Assess blood glucose and gluconeogenesis
How does short term overfeeding affect response to satiety hormones?
Overfeeding:
Reduced glucose uptake in response to insulin
Decreased inhibition of glucose production in response to insulin
Leptin did not increase glucose production from fat stores
No decrease in food consumption either
Overeating reduces sensitivity to satiety hormones
What’s gone wrong with our energy homeostasis
Ghrelin – reduced but still there in obesity
Leptin resistance
Fat not turned into glucose for use
BBB (max out leptin transporter)? Aging?
Insulin resistance
Cannot store glucose as well, and do not maintain glycogen
Still some orexigenic signal but not satiety signals
Combo with palatable food = obeisity
The selfish brain (brain pull) hypothesis
Background
World-wide surge in obesity and diabetes threatening longevity
Link between chronic stress and obesity
Pathophysiology of obesity has to do with a number of hormonal mechanisms
Ghrelin
Leptin
Insulin
Interaction between HPA hormones and feeding behavior?
CNS has 2% of body mass but accounts for 50% of total body glucose usage
100g of glucose per day
Will not use fatty acids or amino acids unless desperate, NEEDS glucose
Neuroglycopenia
Increased heart rate, light headed, irritable, confusion, emotionality, focal seizures
GABA inhibition of neurons throughout brain to reduce energy requirements
KETO FOG!!!
Glucose is hard to store…
How can the brain guarantee supply?
Glucose in the CNS
Cellular mechanism via glutamate
Glutamate uptake by astrocytes in synaptic cleft
One molecule of glutamate = one molecule of glucose via GLUT1 transporter
Glucose in circulation is limited
Circulating glucose can be as low as 5g
Two main mechanisms for brain to ensure glucose availability:
(1) Prevent glucose loss to peripheral tissues (glycolysis) and
(2) stimulate glucose production in liver (gluconeogenesis)
Endocrine and CNS input control glycolysis and gluconeogenesis
Eating behaviour: regulated by paraventricular hypothalamus (where HPA originates)
-Input from hippocampus: memory allows us to prepare for energy demands (using our past experience to estimate the amount needed)
GR receptors in PVN and hippocampus – stress interacts with feeding
PVN: Cross-link to HPA, SNS
ACTH, cortisol and adrenaline:
suppress insulin secretion, induce insulin resistance, and stimulate gluconeogenesis (‘cerebral insulin suppression’)
Energy on request (‘brain-pull’ system)
We will pull for sugar based on the stress in the environment
Push and Pull of the Brain
If (perception of) insufficient glucose neuroglucopenia commences
Activation of hypothalamus (lateral)
This simulates food intake behaviour
Release of other feeding hormones stimulate appetite and eating
‘body pull’
Stress should specifically increases carbohydrate consumption
Fast access to glucose to meet brain need
Can be tested!
Psychological stress and brain pull
These days most of our stressors are psychological
The brain and the body do not need energy to deal with them but they hijack the system
The result is excess carb eating which increases blood sugar
Is not actually needed
So comfort eating makes us fat
Brain pull comfort eating study
Use a within participate study (the same people in the stress/no stress conditions)
G1: Rich buffet
G2: Salad
G3: Dextrose infusion
G4: Lactate infusion
DV1: Measure of SNS activity
Increased in stressor groups with TSST but not non stressed groups
DV2: Keto fog
(1) Stress in all four groups caused increase in neuroglycopenic symptoms
(2) Evidence for brain pull in response to psychological stressors
(3) Alleviated following meal in all groups except meagre salad
All bar salad had fast-available brain energy substrates. Stress fog was only brought back to baseline by sugaror other brain energy substrate.
DV3: Blood Glucose
Blood glucose goes up after a stressor even if you did not eat because the stressor causes release of glucose from stores to blood because of brain pull
Evidence for brain pull in response to stress
DV4: What food did the buffet group eat?
No difference in protein, fat or energy consumed between the stressed and non stressed buffet groups. Sig difference in carbs, the stressed group chose to eat more carbs.
DV5: Depressed mood
Depressed mood is a symptom observed in all groups following stressor
Improves when blood sugar up, artificially or with food
DV6: Perception of Stress
Eating is better than artificial sucrose augmentation for stress
You get lower subjective stress among those who ate vs sugar infusions alone
Eating food reduces perception of stress
Conclusions from our selfish brain
When stress systems activated brain pull mechanisms exceed levels the body can meet
Brain activated feeding behaviour so blood stream has glucose to meet potential demand
High levels of energy available but not needed for psychological stressor
When no physically demanding stressor stored as fat
Once start overeating feel better
- Classical conditioning as well as brain pull leads to excess eating
- Repeated overeating + stress means insulin and leptin resistance
All add to make a fatty a fatty
