Control of food intake Flashcards
What enables storage of food in the stomach?
Autonomic system enables the storage of food in the stomach
What part expands during accommodation?
Fundic part expands when accommodating
What are the control factors of accommodation?
VIP and NO are accommodation control factors
What hormone is important in emptying and why?
Ghrelin because it is Important in initiating the feeling of hunger
What is NO?
A relaxation factor
What is the relaxation of fundus mediated by and how many types can it be differentiated into?
Mediated by reflexes and can be differentiated into 3 types
Name the 3 types of reflexes involved in the relaxation of the fundus and one component mediator
o Receptive (mechanical stimulation of pharynx – mechanoreceptors, sight) o Adaptive (vagal innervation (NO/VIP), tension of stomach) o Feedback (nutrients, CCK)
What are the receptive, adaptive and feedback-relaxation mediated by
mediated by non-adrenergic, non-cholinergic (NANC) mechanisms (i.e., inhibition involving NO, VIP, etc.) as well as by reflex chains involving release of noradrenaline.
What is PACAP isolated from and what is it shown to stimulate?
o Isolated from pituitary and shown to stimulate adenylate cyclase activity in the anterior pituitary
Levels of PACAP in the body
High levels in the brain but also found in the gut
What does PACAP mediate?
o Mediates neuronal regulation of gastric acid secretion; intestinal motility
What does PACAP stimulate?
o Stimulates relaxation of colonic smooth muscle and stimulates pancreatic secretions; stimulates insulin and glucagon secretion in humans.
What does vagotomy impair?
Impairs accommodation and emptying
What is vagotomy a cause for in some patients?
- A cause for early satiety in some patients
What does vagotomy reduce?
- Vagotomy reduces accommodation and gastric compliance
What can prior gastric surgery to vagotomy result in?
- Prior gastric surgery may result in gastroparesis
What is gastric compliance?
Accommodation and perception of distention
Define hunger
-Discomfort caused by a lack of food and the desire to eat
Define appetite
-Desire to satisfy the body’s need of food
Define aphagia
-Inability or refusal to swallow
Define hyperphagia
An abnormal desire for food
What type of control is food intake?
Hypothalamic control
What are the reasons for difference in BMI?
- Genes(70%)
- How much we eat and its composition
What, in the hypothalamus, regulates feeding?
- The balance of stimulating and inhibiting forces in the hypothalamus regulates feeding
How does the hypothalamus control hunger?
Base of the hypothalamus has several nuclei that regulate energy homeostasis
What neurotransmitters have been found in the hypothalamus?
- Orexigenic and Anorexigenic neurotransmitters have been found in the hypothalamus
What do orexigenic neurotransmitters do?
Increase appetite
What do anorexigenic neurotransmitters do?
Decrease appetite
What is feeding behavior/food intake modulated b?
Modulated by hypothalamic sites
What is the lateral hypothalamus(LH) the site of?
-Hunger centre
What is the ventromedial nucleus(VMN) the site of?
-Satiety centre
What does VMN have the ability to restrain and what does this lead to?
– Have the ability to restrain feeding if required; lesion →↑ appetite, with weight gain that tends to persist
What does DMN modulate?
Modulates energy intake(hunger center)
What is released into DMN and what does this increase?
– Release NPY into DMN and increase feeding
What does PVN modulate?
Modulates feeding behaviour
What does PVN control?
Control feeding behaviour
What do NPY, opiods, GABA increase?
Increase feeding
What does leptin do to food intake?
Decreases food intake
In the arcuate nucleus, what do the neurons produce?
Neurons produce orexigenic signals(NPY, the opioids, dynorphin, β-endorphin, POMC, galanin, amino acids, and glutamate)
What is the SCN responsible for?
responsible for controlling circadian rhythms
Where is the SCN located?
In the hypothalamus
What is the SCN directly above?
directly above the optic chiasm
What is the medial amygdaloid nucleus a sub-region of?
Sub-region of the amygdaloid complex
What does a medial amygdaloid nucleus participate in?
Participates in the regulation of food intake
– 5-HT (via 5-HT2C and 5-HT1A): regulates appetite and food intake
How is appetite regulated?
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 alpha-melanocyte stimulating hormone (alpha-MSH)
Steps involved in appetite stimulating pathway
o The appetite suppressing neurons make the precursor pro-opiomelanocortin (POMC), which is broken down into alpha-MSH, which in turn binds to melanocortin 4 receptors (MC4R) to suppress appetite. Shown here is no occupancy of MCR4 receptors by alpha-MSH, and thus stimulation of appetite.
Steps involved in appetite repressing pathway
A serotonin 5HT2C agonist, such as meta-chlorphenylpiperazine (mCPP), hypothetically binds to 5HT2C receptors on POMC neurons in the appetite suppressing pathway, activating POMC neurons and leading to release of alpha-melanocyte stimulating hormone (alpha-MSH), which binds to melanocortin 4 receptors (MC4R) to suppress appetite.
What does zimelidine do?
inhibits the reuptake of 5-HT from synaptic cleft, so 5HT persists and able to mediate its effects in suppressing appetite
What are the side effects of zimelidine?
Side effects are dry mouth, increased sweating (hyperhidrosis), vertigo, nausea,
What is the role of the prefrontal cortex?
Integration of sensory information from inside and outside the body
What dose the prefrontal cortex receive and from where?
– Receive emotional and cognitive information from the limbic system
What is the limbic system?
complex system of nerves and networks in the brain; areas concerned with instinct and mood. May control emotions, pleasure (fear, anger, etc.)
What is the MeA and what has it been described as?
- The medial amygdaloid nucleus (MeA) is a sub-region of the amygdaloid complex that has been described as participating in regulating food intake
What is serotonin known to play as?
o Serotonin (5-HT) has been known to play an important role in regulating appetite and food intake.
What is the cortico-limbic mechanism of reward under control of?
Under executive control of the prefrontal cortex
What is the control of food intake an integration of?
Integration of many signals
What does DMN modulate?
Modulates energy intake
What does the destruction of DMN lead to?
Destruction leads to hyperphagia & obesity
What does the DMN also recieve and also has what type of cells?
DMN also receive projections from agRP/NPY neurons from ARC; it also has NPY-expressing cells
What is the PFA?
A very sensitive hypothalamic site for NPY-induced eating
How is NPY found?
NPY is found in high concentrations within neurons of hypothalamus
What happens of NPY is injected into the hypothalamus?
if injected into the hypothalamus, it stimulates powerful stimulus to eat
What is the FX and what does it carry?
C-shaped bundle of nerve fibres in the brain that carries signals from the hippocampus to the mammillary bodies and then to the anterior nuclei of thalamus
What system is FX part of and what is it involved in?
It is part of the limbic system – involved in memory and recall
What is the LHA?
Hunger center
What is the VMN?
Satiety center
What is the ME part of and what is it integral to?
- Part of hypothalamus
- Integral to the hypophyseal portal system
What does the stimulation of ventromdial wall of paraventricular nucleus lead to?
Leads to aphagia
What do lesions of ventromedial wall of paraventricular nucleus lead to?
Lead to hyperphagia
What does the brain contain?
Has glucostats
What is the lateral hypothalamus the center of?
Feeding center
What does lesions of the lateral hypothalamus lead to?
Aphagia
What do opioids and growth hormones do to appetite?
Increase appetite
What is Naltrexone?
An opioid antagonist
What does Naltrexone reduce?
Reduces the positive hedonic valence of food
What does removal of lateral hypothalamus cause and lead to?
Causes hypophagia, leading to death due to severe weight loss
What dose the removal of the ventromedial hypothalamus cause and lead to?
Causes hyperphagia, leading to weight gain and severe obesity
What signals control nutrient intake?
Signals from periphery and CNS control nutrient intake
What factors affect if food is sought or not?
- Food preferences
- Emotions
- Environment
- Life style
- Circadian rhythm – limits food intake to certain times (in some people)
What does blood glucose concentration stimulate?
Stimulates gluco-receptors in hypothalamus
What does a decrease in blood glucose concentration lead to?
Leads to up-regulation of hunger
What does an increase in blood glucose concentration lead to?
Leads to up-regulation of satiety
Why do diabetic patients feel hungry despite an increase in blood glucose concentration?
• Cold environments stimulate feeding while hot environments inhibit appetite
What does distension of a full stomach inhibit?
Inhibits appetite
What does the contraction of an empty stomach stimulate?
Stimulates appetite
What does insulin decrease?
Insulin decreases feeding behavior
What are people that are suffering with IDDM?
They are hyperphagic and such individuals are not obese because insulin is required for adipocytes to store fat
What does calcitonin reduce?
Reduces appetite.
What does insulin inhibit?
Inhibits lipolysis in adipocytes
What induces lipolysis?
- Ghrelin, NA, adrenaline, growth hormone, testosterone and cortisol induce lipolysis
What are insulin, glucagon and amylin secreted from and what do they participate in?
- Insulin, glucagon and amylin are all secreted from the endocrine pancreas, and all participate in the regulation of energy homeostasis
Where does insulin act at and what does it do ?
o Insulin acts at both the liver and the forebrain to reduce energy intake as well as to suppress hepatic glucose production.
Where does glucagon mainly act at and what does it do?
o Glucagon acts mainly at the liver where it increases glucose production while generating a signal to reduce energy intake that is relayed to the hindbrain.
Where does amylin directly act and to do what?
o Amylin acts directly at the hindbrain to reduce energy intake
What does fat ingestion cause the release of?
• Fat ingestion causes CCK release and the slowing of gastric emptying (sense of fullness)
What does CCK and somatostatin inhibit?
inhibit further food intake; satiety factors
What does an injection of CKK in the brain reduce?
Reduction of appetite
What do leptin and ghrelin act on?
• Leptin and ghrelin act reciprocally on food intake
What does the stimulation of their receptors in hypothalamus change?
Changes in food intake
Where is leptin found?
Found in white adipose tissue
What does leptin control?
Controls fat stores by operating a feedback mechanism between adipose tissue and brain
What happens as adipose tissue size increases?
Increase in leptin secretion
How do insulin and leptin act and via what?
- Insulin and leptin act agonistically in reducing food intake via action on receptors within the brain
What does satietin suppress and without causing what?
- Satietin suppresses food intake and weight without causing conditioned taste aversion
What pathway prevails when there’s an abundance of leptin or insulin?
- The anorexigemic pathway prevails:
- Increase of energy expenditure
- Increase of thermogenesis
- Diminished food intake
What does decreasd petin and insulin serum concentrations lead to?
Lead to activation of orexigenic pathways:
- Low metabolic rate
- Enhanced appetite
Where is the leptin gene mainly expressed?
Expressed mainly in adipocytes
What can administration decrease, induce and increase?
• Administration can decrease food intake, induce weight loss and increase energy expenditure
Who does hyperphagia and severe obesity occur in?
• Hyperphagia and severe obesity occurs in in humans with leptin deficiency or leptin receptor defects
What does leptin increase the expression of?
• Increases the expression of anorexigenic factors (pro-opiomelanocortin (POMC), cocaine-and amphetamine-regulated transcript (CART), corticotrophin-releasing hormone (CRH), neurotensin)
What does leptin stimulate?
Stimulates metabolic rate
What does leptin inhibit, which goes on to stimulate what?
• Inhibits neuropeptide Y, which stimulates feeding
Can one be resistant to the effects of leptin?
• Yes; → binge eating, despite adequate or growing adipose tissue (obese)
What is ghrelin?
An appetite inducing hormone
How does Ghrelin act and what does it stimulate?
Fast-acting and stimulates food intake
What is ghrelin released by?
- Released by stomach, pancreas, adrenals in response to nutritional status
When do ghrelin levels increase and decrease?
Increase preprandially and decrease after a meal
What does ghrelin increase?
- Increases central orexins
How can ghrelins secretion be inhibited?
- Its secretion can be inhibited by leptin
What is ghrelin produced by and where in the stomach?
- In the stomach, ghrelin is produced by cells called P/D1 cells in the upper section of the stomach
What inhibits the expression of ghrelin ?
Increased levels of glucose inhibits its expression in the P/D1 cells
What is Obestatin produced by?
Produced by epithelial cells of the stomach
What is Obestatin encoded by?
• Encoded by ghrelin gene
What does Obestatin oppose?
Opposes effect of ghrelin on food intake
What does Obestatin suppress?
Supresses food intake
What does Obeostatin antagonize?
• Antagonises ghrelin-induced food intake (and growth hormone secretion)
An imbalance of what has a role in obesity?
• Imbalance of ghrelin and obestatin has a role in obesity
What does Obestatin mediate its effect via?
Obestatin mediates its effects via different receptors to ghrelin
