Week 10: Regulation Of Metabolism And Feeding Flashcards
Define Caloric homeostasis
Maintenence of energy balance in the body. Preserves cellular metabolism; we store energy for when food is scarce and bridge gaps between meals
Define Orexigenic
Appetite stimulating
Define Anorexigenic
Appetite inhibiting
Define Anabolic
Building/storing
Define Catabolic
Breaking down/ using
Define prandjal
Relating to meals
Define phagia
(Suffix) to eat
What is Adiposity?
Amount of body fat
What does Hunger and satiation govern?
Meal-by-meal eating behaviour
What does hypothalamic circuitry coordinate?
Daily food intake With long term, homeostatic, and feedback regulation of energy balance and body weight
What is Prandial or Fed state?
Insulin promotes use and storage (anabolic)
Postabsorptive or Fasted state?
Absence of insulin; mobilisation of stores (catabolic)
What does liver do?
Oxidizes many lipids Stores carbohydrates
What do most tissues e.g. muscles do?
Oxidise glucose or lipids
What does CNS do?
Oxidises mainly glucose
What does adipose tissue do?
Stores lipids
What is the cephalic phase?
Hypothalamus drives the parasympathetic NS stimulation of pancreatic insulin secretion
What is the GI phase?
Gut hormone stimulate insulin secretion
What is substrate phase?
Insulin secretion stimulated by metabolites (glucose)
What is the gastric signal?
Stomach distension - vagus nerve > nucleus tracts solitarius ( NTS)
What are the post-gastric signals (I.e. intestinal)
Cholecystokinin Glucagon-like peptide-1 (GLP-1) / peptide YY (PYY) Liver signals Increased plasma osmolality
Cholecystokinin
Enteroendocrine cells secrete CCK when fatty acids are detected - acts in vagus (synergises with stretch) - hormonal and neural
GLP-1/ PYY
Taste carbohydrates in gut, GLP-1 increases insulin secretion and both act centrally - hormonal
Liver signals
Detect absorbed nutrients/insulin - satiation signals via vagus - neural
Increased plasma osmolality
Sensors in brain (caudal brainstem) or viscera
When do meals terminate?
Before nutrient homeostasis occurrs
What happens when satiation signals disappear?
Hunger can re-emerge and another meal is initiated
What are the internal hunger and satiation signals?
Hunger pangs/ stretch Various blood chemicals relating to body state including insulin, glucose, CCK, GLP-1, ghrelin, osmolality
What are the internal contextual factors?
Mood; habit; memory
What are the external quality cues?
Appearance and smell of food
What are the external context cue ?
Safe time to eat Social setting Cultural factors Time of day
What are the internal hunger and satiation signals?
Hunger pangs/ stretch Various blood chemicals relating to body state including insulin, glucose, CCK, GLP-1, ghrelin, osmolality
What are the internal contextual factors?
Mood; habit; memory
What are the external quality cues?
Appearance and smell of food
What are the external context cue ?
Safe time to eat Social setting Cultural factors Time of day
What are two physiological functions of body weight?
Food intake Intestinal absorption
The brainstem mediated important reflexes via what route?
Dorsal Vagal Complex (DVC) Parabrachial nucleus (PBN)
What are higher centres required for?
Modification and integration of signals Learning, adipocyte factors and circadian rhythms (daily cycle)
What does the reflex arc act to modulate?
Absorption and incorporation of other metabolites
What is the NTS closely associated with?
Dorsal Medial vagus Area postrema
What does the reflex arc act to modulate?
Absorption and incorporation of other metabolites Allow more or less food to be absorbed at the hypothalamus levels
What is the NTS closely associated with?
Dorsal Medial vagus Area postrema
What is satiation signals associated with?
Body weight (adipocyte)
What does Adiposity influence?
Food intake indirectly
What is the main centre for control of body weight?
Hypothalamus
What is Leptin?
A satiation signal of Adiposity
What does Leptos mean?
Thin
What happens if there is a genetic mutation in the peptide ob/ob or its receptor db/db?
are obese
What happens to tissue if someone has more adipose tissue?
The tissue is less responsive to insulin
What effect does leptin and insulin have?
Catabolic effects on metabolism
What is Ghrelin?
Hunger signal
What is ghrelin and where is it secreted from?
Peptide and by the stomach during fasting
When is Ghrelin secreted?
Just prior to meals suggesting it has a role in the initiation of meals
What does Ghrelin affect?
Dopamine reward pathways
What does levels of Ghrelin correlate with?
Hunger scores
What is hyperphagia?
Abnormally great desire for food
What is hypophagia?
Reduction in food intake and eating behaviour
What is dorsomedial involved in?
Circadian rhythms Feeding (inhibition) Emotions
What is ventromedial involved in?
Inhibits feeding (satiety centre)
What is the Lateral hypothalamic area Involved in?
Eating, drinking
What does VMH lesions disrupt?
Autonomic tone - decreasing sympathetic/ increasing parasympathetic, Vagal tone
What does LHA lesion disrupt?
Sensorimotor integration - reward and motor systems
What is the main centre for appetite regulation?
Arcuate nucleus
What 2 neurones are key to regulation of food intake and metabolism?
Dopamine neurons GHRH
What is the precursor for melanocortin peptides (alpha MSH)?
Pro-opiomelanocortin (POMC)
Where does POMC act on?
Melanocortin receptors (e.g. MCR4)
What does POMC play an important role in?
Inhibit feeding (anorexigenic effects)
What does deficiency of POMC lead to?
Hyperphagia and obesity
Where are melanocortin receptor 4 found in?
Numerous projection sites of Arcuate POMC neurons
What is MCR4 expresses by?
PVH neurons which surpresses food intake
What does melanocortin stimulation of MC4R cause?
Increase in energy expenditure and maintain glucose homeostasis
What does genetic deletion of MC4R in life and human result in?
Severe hyperphagic obesity
What is neuropeptide Y?
Orexigenic - effects lasts 1-2 hours
What does agouti-related peptide have?
Longer acting Orexigenic effect; acts as a melanocortin receptor antagonist
What does injection of NPY into the PVN cause?
Increased food intake and negatively controls sympathetic outflow Directly inhibits MC4R expressing cells
What does ablation of NPY/AgRP In adults result in?
Profound decrease in food intake and body weight
What are satiety signals?
Both hormonal and neural
Where does bidirectional flow of information occur?
Brainstem and hypothalamus
What does leptin/insulin in Arcuate nucleus stimulate?
POMC anorexigenic cells Inhibits NPY/ AGRP Orexigenic cells
What does low level of insulin and leptin release?
NPY/AgRP/GABA cells from inhibitory satiety Control
What stimulates feeding behaviour?
High Ghrelin levels from Vagal input and hypothalamic circuits
What is Lateral hypothalamic area?
Orexigenic site - driving feeding as well as central to anabolic effects
Where does the enteroendocrine peptides act on?
ARC system
What are other satiety factors ?
GLP-1 and PYY
What does GLP-1 and PYY act ?
Stimulate POMC and inhibit NPY cells
What has therapeutic potential in obesity treatment?
GLP-1 agonists
What does global deficiency of 5-HT2C or 5-HT1B receptors result in?
Hyperphagia Obesity Disturbed glucose homeostasis
What is mood controlled by?
Serotonergic systems
What is serotonergic systems?
Implication for interaction of mood with eating behaviours
What does low level of insulin and leptin release?
NPY/AgRP/GABA cells from inhibitory satiety Control
What stimulates feeding behaviour?
High Ghrelin levels from Vagal input and hypothalamic circuits
What is Lateral hypothalamic area?
Orexigenic site - driving feeding as well as central to anabolic effects
Where does the enteroendocrine peptides act on?
ARC system
What are other satiety factors ?
GLP-1 and PYY
What does GLP-1 and PYY act ?
Stimulate POMC and inhibit NPY cells
What has therapeutic potential in obesity treatment?
GLP-1 agonists
What does global deficiency of 5-HT2C or 5-HT1B receptors result in?
Hyperphagia Obesity Disturbed glucose homeostasis
What is mood controlled by?
Serotonergic systems
What is serotonergic systems?
Implication for interaction of mood with eating behaviours
What is found in Paraventricular nucleus?
Oxytocin (OXY) Corticotropin releasing hormone (CRH) Both peptides are anorexigenic
What does OXY mediate?
CRH effect and stress related decrease in eating
What does CRH mediate ?
Increase in sympathetic activity
What is involved in Lateral hypothalamic area?
Orexin Melanocortin concentrating hormone (MCH) - they are orexigenic
What does orexin cause?
Wakefulness It’s decrease after eating inside drowsiness
Where does area postrema lie?
Caudal end of the 4th ventricle adjacent to the nucleus of tractus solitarus, not connected to the hypothalamus
Where does area postrema get information from?
Blood and transfers that information into dorsal vagal complex (DVC)
What does area postrema detect?
Toxins
What does dorsal motor nucleus of vagus control?
Parasympathetic output
Where is the input from hypothalamus Via?
Paraventricular nucleus to sympathetic preganglionic neurons in spinal cord
What is the main centre for appetite regulation?
Arcuate nucleus
Where is arcuate nucleus found?
Median eminence
Connecting hypothalamus to pituitary gland
What does dopamine neuron do?
Inhibit prolactin secretion
What does GHRH cause ?
Pulsatile release and growth hormone secretion
What are key regulation of food intake and metabolism?
Dopamine neurons
GHRH
Where is the brainstem involved through?
Dorsal vagal complex
Parabrachial nuclei around superior cerebellar peduncle
What does brainstem centre allow?
Reflexive eating behaviours
Distinguishing whether something is good or bad to eat
Recognise how much glucose and salt there are in the bloodstream
Decerebrate rat
Do not have cortical input
Distinguish between bitter, salty, sweet flavours and eat accordingly
They don’t eat as much bitter - toxic substance
Where does afferent input go to?
Nucleus tract of solitarus
What does reflex arc act to modulate?
Absorption and incorporation of other metabolites
What is NTS closely associated with?
Dorsal medial vagus
Area postrema
Where is food mainly absorbed by body?
Small intestine (duodenum)
What happens after we’ve eaten?
Glucose is absorbed into the blood
Travel to the liver
The liver store glucose as glycogen
What is the role of insulin
Stimulate glucose uptake to liver by the blood indirectly
Insulin inhibit secretion of glucose to the blood from liver
Stimulate uptake of glucose to adipocyte to produce more triglyceride
Stimulate uptake glucose to skeletal muscles
What does body absorb?
FA
AA
Monoglyceride
Stored as glycogen, protein and triglyceride
Fed state
Gluconeogensis
Lipogensis
Protein synthesis
What does liver have?
Short term capacity
Releases glucose by breaking down glycogen stores
Produced ketone bodies
When is insulin released?
In the presence of glucose in the body
There are low levels of glucose before meals
What is insulin release?
Biphasic
What is cephalic Phase activated by?
Thought
Smell
Taste
Sight of food
What is the cephalic phase mediated by?
Cholinergic/vagal mechanism Via parasympathetic
What does meals generate?
Satiation signals
What does stomach have and what does liver release?
Stomach - stretch receptors
Liver releases CCK, GLP-1
What are adipocyte signal?
Leptin
Insulin
What does receptors on stomach fire?
Signals to the brain which say that the stomach is full which inhibit feeding
Activating ventromedial hypothalamus
What are CCK and GLP1 releases in proportion to?
Content of fat and protein
What does leptin level indicate?
How much fat you have stored in adipose tissue
The more fat, the higher the leptin level
What does sight, taste and smell override?
Biochemical signal and it can cause you to eat more quickly
What is satiation signal associated with?
Body weight (adipocity)
Scientific approach to obesity
Lack of will power
Lifestyle/environment
Biology/genes
What does elevated extracellular glucose level activate?
POMC Neurons
What does POMC neurons produce?
Anorectic peptide alpha-melanocyte by posttranscriptional processing of POMC
What is alpha-MSH
Main peptide involved in appetite regulation
What does alpha-MSH bind to?
Melanocortin receptor 3 and 4 on second order neurons and activate catabolic pathways
Reduced food intake
Increased energy expenditure
What does endorphin modulate?
Reward system
