control of food intake Flashcards
What organs make up the GI tract?
• Mouth • Oesophagus • Stomach • Small intestine • Large intestine • Anus Note: the liver, pancreas and gallbladder are part of the digestive system but DO NOT form the GI tract
How is the food stored in the stomach?
ANS (autonomic nervous system) enables the storage of food in the stomach
What are the 3 control factors important for accommodation (decrease in gut motility)?
VIP (vasoactive intestinal peptides)
NO (nitric oxide)
PYY secreted by the pancreas
What is the 1 control factor important for emptying of the GI tract, which results in the feeling of hunger?
Ghrelin
What is Ghrelin?
Ghrelin is secreted by the stomach fundus and increases the sense of hunger and stimulates gastric emptying
There are many mediators involved in the relaxation of the stomach during accommodation. Describe these mediators and their mechanisms in detail.
The relaxation of the gastric reservoir is mainly regulated by reflexes. Three kinds of relaxation are:
1. Receptive relaxation (from mechanical stimulation of the pharynx mechanoreceptors)
2. Adaptive relaxation (inhibitory vagal fibre via NANC inhibition)
3. The inhibitory vagal fibres release Ach, activating inhibitory pathways which release NO, PACAP, VIP, and/or ATP in order to relax
Feedback relaxation (CCK and nutrients)
What is a vagotomy?
a surgical operation in which one or more branches of the vagus nerve are cut, typically to reduce the rate of gastric secretion (e.g. in treating peptic ulcers).
This process reduces:
• Accommodation
• Gastric compliance
What are potential changes that occur in the functioning of the GI tract due to a vagotomy?
• Nausea • Easy filling • Bloating • Early satiety However, this is not common due to the fact that satiety is controlled primarily by the ANS rather than the physical size of the stomach.
Define hunger
it is the discomfort caused by the lack of food and the desire to eat - a strong craving/ drive for food/ sensation of emptiness in the stomach
Define appetite
the desire/ desire to satisfy the body’s needs for food - a hunger-stimulated response
Define satiety
the state of being full after eating food (joyous moments - no longer need to continue eating)
Define aphagia
The inability or refusal to swallow
Define hyperphagia/polyphagia
An abnormal desire for food (extreme unsatisfied drive to eat)
Hunger, satiation and satiety are cues that tell you when to start and stop eating
• Hunger tells you to start eating
• Satiation tells you to stop eating
Satiety is the satisfaction between meals
Give a summary of the factors that influence food intake
Hypothalamic control: balance of stimulating and inhibiting forces in the hypothalamus regulates feeding
What is the reason for people having different BMIs?
- Genes accounts for 70% of the reason
2. How much we eat and its composition
What factors are appetite influenced by?
• Family gatherings
• Food palatability (food preference)
• Emotional (stress, anxiety, depression)
• Habitual (lifestyle)
• Environment
• Circadian
Limits food intake to certain times (in some people)
Explain the mechanism by which the hypothalamus controls food intake
The hypothalamus is the control centre for appetite and food intake (controls hunger and thirst)
The base of the hypothalamus has several nuclei that regulate energy homeostasis. This controls the appetite, size of helping and our ingestive behaviour
What is the role of the prefrontal cortex and limbic system in the control of food intake?
Pre frontal cortex: food-seeking
• Integration of sensory information from inside and outside the body
• Receives emotional and cognitive information from the limbic system
• Helps one to make choices by translating all of the homeostatic and environmental information into adaptive behavioural response
Limbic system: complex system of nerves and networks in the brain; areas concerned with instinct and mood. May control emotions such as pleasure, fear, anger etc
• The satiation of feeding behaviour is associated with motor planning and execution
Cortico-limbic mechanisms of reward are under executive control
What is the limbic system?
This is a complex system of nerves and networks in the brain. It involves area around the cortex concerned with instinct and mood.
It has control over the following emotions: fear, pleasure, anger; it also drives hunger, sex, dominance, care of offspring, etc.
Feeding behaviour/food intake is modulated by many hypothalamic sites.
List some of them
1) Lateral Hypothalamus (LH) = hunger centre
2) Ventromedial Nucleus (VMN) = satiety centre
Ventromedial nucleus and lateral hypothalamus
• Has the ability to restrain feeding if required
3) Dorsomedial Nucleus (DMN) = modulates energy intake (hunger centre)
releasing NPY into the DMN = increases feeding
4) Paraventricular Nucleus (PVN) = modulates feeding behaviour
Paraventricular nucleus and perifornical hypothalamus
• controls feeding behaviour
• NPY, opioids, GABA etc increases feeding
• Leptin decreases food intake
5) Arcuate Nucleus (ARC) neurons produce orexigenic signals: • NPY • Opioids • Dynorphin • B-endorphin • POMC • Galanin • Amino acids • GABA Glutamate
What can a lesion of the VMN result in?
Increases appetite
Weight gain that tends to persist
Where is the suprachiasmatic nucleus located and what is its function?
Nuclei in the hypothalamus
It is responsible for controlling circadian rhythms
Describe the regulation of appetite in the hypothalamus by the 5-HT2C agonist
Appetite is regulated by the balance between an appetite-stimulating pathway that releases agouti-related peptide (AgRP) and neuropeptide Y (NPY), and an appetite suppressing pathway that releases α-melanocyte stimulating hormone (α-MSH).
The appetite suppressing neurons make the precursor pro-opiomelanocortin (POMC), which is broken down into α-MSH, which in turn binds to melanocortin 4 receptors (MC4R) to suppress the appetite. When there is no occupancy of MC4R receptors by α-MSH, there is stimulation of the appetite.
A serotonin 5-HT2C agonist, such as meta-chlorphenylpiperazine (mCPP), hypothetically binds to 5-HT2C receptors on POMC neurons in the appetite suppressing pathway, activating POMC neurons and leading to the release of α-MSH, which binds to MC4R to suppress the appetite.
Name a 5-HT2C agonist and describe its function in the control of food intake
mCPP (meta-chlorphenylpiperazine)
A serotonin 5-HT2C agonist, such as meta-chlorphenylpiperazine (mCPP), hypothetically binds to 5-HT2C receptors on POMC neurons in the appetite suppressing pathway, activating POMC neurons and leading to the release of α-MSH, which binds to MC4R to suppress the appetite.
Regulation of appetite in the hypothalamus can lead to appetite suppression. Describe the process by which this occurs.
Suppressive pathway = α-melanocyte stimulating hormone (α-MSH)
• mCPP (agonist) binds to 5-HT2C receptor on POMC neuron
• Activates POMC neuron
• POMC neuron releases α-MSH
• α-MSH binds to MC4R
• Suppression of appetite
MC4R occupied by α-MSH = decreased appetite
MC4R NOT occupied = increased appetite
Name 3 anorexigenic factors and state what they do
• 5HT
→ 5-HT2C
→ 5-HT1A
• GABA • Dopamine These decrease appetite
State some diurnal variations that affect the food intake
- Carbohydrates metabolised during the day
- Fats metabolised at night
Hypothalamus responds to the switch between carbohydrate and fat metabolism
Specify where the satiety centre is
Ventromedial hypothalamic nucleus (wall of paraventricular)
What are glucostats?
Glucostatsare special receptor neurons (glucoreceptors to be precise) in the brain that monitor and regulate glucose levels and their fluctuations in the bloodstream
What does stimulation of the ventromedial nuclei in the brain result in?
Aphagia
What does lesions of the ventromedial nuclei in the brain result in?
Hyperphagia (increased appetite/excessive hunger)
Specify where the feeding/hunger/thirst centre is
Lateral hypothalamus
What happens when the lateral hypothalamus of the brain is stimulated?
Increases feeding
What does lesions of the lateral hypothalamus result in?
Aphagia
What is naltrexone?
Opioids are growth hormones that release hormones that result in an increased appetite
Naltrexone is an opioid antagonist that reduces the positive ‘hedonic valence’ of food
Describe the difference between a lesion in the ventromedial and lateral hypothalamic regions of the brain
Lesion in ventromedial hypothalamus = increased appetite
Lesion in lateral hypothalamus = loss of appetite
In terms of the hypothalamus, name a possible cause of an obese rat
Ventromedial hypothalamic lesions
In terms of the hypothalamus, name a possible cause of an anorexic rat
Lateral hypothalamic lesion
Besides the hypothalamus, what other inputs control feeding behaviour?
Orexigenic and Anorexigenic neurotransmitters have been found in the hypothalamus.
Orexigenic neurotransmitters increase our appetite, while anorexigenic neurotransmitter decrease our appetite.
What controls nutrient intake?
Signals from the periphery and CNS control nutrient intake
Note: higher functions modulate responses to both the CNS and peripheral cues in order to inhibit or stimulate food intake
Describe the stimulation of glucoreceptors in the hypothalamus and what regulates this
The concentration of glucose in the blood stimulates glucoreceptors in the hypothalamus
• Low blood glucose = up regulation of hunger
High blood glucose = up regulation of satiety
Why do diabetic patients feel hungry despite high blood glucose?
Insulin resistance
Insulin receptor not functional
No insulin released (type I diabetes)
How does temperature of the environment control food intake?
Cold environments stimulate feeding
Hot environment inhibit appetite
Describe the role of gut hormones in the control of food intake
- Fat ingestion causes CCK release and the slowing of gastric emptying (sense of fullness)
- CCK (released from I cells in the intestines or nerve endings) and somatostatin are satiety factors that inhibit further food intake
- Injection of CCK in the brain = reduction of appetite
Where is CCK released from?
I cells in the intestines release CCK
What is the role of pancreatic hormones in the control of food intake?
- Pancreas releases insulin in direct proportion to the amount of fat stored in white adipose tissue
- This insulin travels in the blood to the brain capillaries
- Insulin transporter transports insulin from brain capillary –> brain
- This insulin released into the brain acts on insulin receptors on neurons
- This can lead to anabolic activity or catabolic activity
Name 3 anorexigenic agents
- Insulin
- Glucagon
- Amylin
Describe how anorexigenic agents such as insulin, glucagon and amylin contribute to the control of food intake
The pancreas releases insulin and glucagon directly to the liver where it can then relay the message to the hindbrain = increase satiety = decrease food intake
The pancreas also releases amylin directly to the hindbrain = increase satiety = decrease food intake
Where is leptin expressed?
Mainly in adipocytes
How can leptin contribute to weight loss?
Administration can decrease food intake, induce weight loss and increase energy expenditure
What is the role of leptin in the control of food intake?
White adipose tissue secretes leptin in direct proportion to the amount of white fat (more white fat = more leptin secretion). Leptin controls fat stores and feeding behaviour by operating a feedback mechanism between adipose tissue and brain.
Inhibits feedings
What is the mechanism by which leptin controls food intake?
• Increases the expression of anorexigenic factors:
→ POMC: pro-opiomelanocortin
→ CART: cocaine and amphetamine-regulated transcript
→ CRH: corticotrophin-releasing hormone
→ Neurotensin
· Stimulates metabolic rate
Inhibits NPY which stimulates feeding (therefore overall effect is inhibits feeding)
Can someone be resistant to the effects of leptin?
· Binge eating, despite adequate or growing adipose tissue (obese)
· Hyperphagia and severe obesity occurs in humans with leptin deficiency or leptin receptor defects
High correlation of leptin levels with body fat in humans and animals
What is ghrelin?
A fast acting appetite inducing hormone (orexin) = stimulates hunger
Where is ghrelin released from?
HINT: SAP
· Stomach
· Pancreas
· Adrenals
Released in response to nutritional status
How does ghrelin stimulate hunger?
Levels of ghrelin increase before meals and decrease after meals
· Ghrelin increases central orexins (NPY and AgRP)
These are hunger signals
Ghrelin suppresses the ability of leptin to stimulate anorexigenic factors
What is the association between ghrelin and leptin?
Leptin = inhibits feeding
Ghrelin = stimulates feeding
Leptin and Ghrelin act reciprocally on food intake, via stimulation of their receptors in the hypothalamus
Secretion of ghrelin can be INHIBITED by leptin
What is obestatin released by?
Produced by epithelial cells of the stomach
Encoded by ghrelin gene but it opposes the effects of ghrelin on food intake
What is the effect of obestatin in the control of food intake?
Obestatin mediates its effects via different receptors to ghrelin
· Suppresses food intake = less body weight gain
Antagonises ghrelin-induced food intake and growth hormone secretion
What can result from an imbalance of ghrelin and obestatin?
May have a role in obesity
Decreased Ghrelin: Obestatin ratio characterises obesity in women
