LT2 Hypothalamus Flashcards
Why is it not just genectic mutation/drift that is causing the rapid increase in obesity rates?
Because the timeframe is too quick for it to be caused by genes alone
What is the % of heritability of fat mass?
40% to 70%
Give an example of one monogenetic mutation that causes obesity
Leptin and leptin receptor mutation
Define polygenic aetiology
A characteristic that is influence by two or more genes
What are our survival genes likely to do?
Drive obesity
Why are our survival genes likely driving obesity?***
Why is it difficult to lose weight, once gained?
Increased body fat alters brain function
Brain views extra fat as normal so dieting is seen as threat to body survival
Body defends heavier weight
CNS influence energy balance and body weight by what 3 mechanisms?
Behaviour = feeding and physical activity
ANS activity = regulates energy expenditure
Neuroendocrine system = secretion of hormones
Why is obesity a disease of the brain?
CNS controls energy intake and body weight
Brain integrates signals
What is the main CNS centre responsible for energy intake control?
Hypothalamus
What is the satiety centre in hypothalamus?
Ventromedial hypothalamus
What is the hunger centre in hypothalamus?
Lateral hypothalamus
What happens when ventromedial hypothalamus is removed?
Causes obesity because satiety signals not received
What happens when lateral hypothalamus is removed?
Causes leanness because hunger signals are not received
Why is an individuals weight stable over lengthy periods of time?
Because energy balance is controllled by feedback loops
They act to maintain constancy of total body energy stores
Why do most people regain weight after stopping dieting?
Because of the feedback loops bringing the body back to usual weight
How is food intake and energy expenditure modulated? (flowchart)
Signals produced in response to body energy status
Sensed by the brain
Signals in brain act to modulate food intake and energy expenditure
Where is the hypoethalamus located?
At the base of the brain, in the diencephalon
Attached above the pituitary gland
Define sagittal section
Vertical slice through the body
Divides it into left and right sides
Name the 6 areas of the hypothalamus
Arcuate nucleus (ARC)
Ventromedial nucleus (VMN)
Dorsomedial nucleus (DMN)
LHA/PFA = lateral hypothalamus / perifornical area
Paraventricular nucleus (PVN)
What is the central role of ARC?***
Nutrient homeostasis = integrate signals
Required for optimal functioning of organism
Define First-Order Neurones
Sensory neurons that detect the stimulus = afferent, PNS
Sensory neurons that pass through a spinal nerve have their cell bodies in the dorsal root ganglion
Define Second-Order Neurones
Interneurons = that relay sensory information from the spinal cord/brainstem to the thalamus and cerebellum
Glutamate (agonist, area effected, effect, half-life)
NMDA
LHA
Stimulates feeding
Lasts less than 10mins = short lasting action
GABA (agonist, area effected, effect, half-life)
Muscimol (GABA_A receptor agonist)
VMN, DMN, or PVN
Stimulates feeding
Lasts about 30mins
Opioids (agonist, area effected, effect, half-life)
B-endorphin, dynophin, long-acting enkelphalin
ARC, VMN, DMN, or PVN
Stimulates feeding
Effects short-lived and modest
Monoamines (agonist, area effected, effect, half-life)
Noradrenaline, dopamine, serotonin
SUPRESS food intake
What system are many anti-obesity drugs developed to act on?
Monoamin system
Why are most anti-obesity drugs withdrawn?
Side effects
Name the neurotransmitters that stimulate feeding and the one that supresses it
Glutamate, GABA, Opioids = stimulate
Monoamins = supress
What is the name for something that increases appetite or food intake and its opposite word
(AN) OREXIGENIC
Name the orexigenic neuropeptides
NPY, MCH, Agouti
Galanin, Orexins, Ghrelin, Endocannabinoids
Name the anorexigenic neuropeptides
α-MSH, CART, GLP-1, TRH, CRH, PYY
Leptin & Insulin (both hormones not neuropeptides)
What 3 things does neuropeptide Y do?
When injected into hypothalamus = stimulates food intake, reduces energy expenditure and induces lipogenic enzymes in fat and liver cells
Where are neuropeptide Y-containing neurones mainly found?
ARC and DMN
What happens with repeated administraiton of NPY to hypothalamus?
Leads to obesity = because stimulates food intake, reduces energy expenditure and incduces lipogenic enzymes
When is NPY gene expression increased?
After fasting or reduce feeding
What are NB mice? And what happens when they lack NPY receptor subtypes?***
These mice lack Y1 or Y5 receptor subtypes.
They are pre-disposed to mild obesity because of functional redundancy and developmental copmensation
What does α-MSH stand for?
α-melanocyte stimulating hormone
What is α-MSH?
Non-opioid peptide
What does POMC gene encode?
α-melanocyte stimulating hormone
What is the role of α-MSH?
Acts in the ARC of hypothalamus = INHIBITS food intake
When is POMC gene expression reduced and increased?
Decreased after fasting
Increased after increase in energy balance
Because codes for α-MSH, which inhibits food intake
What melanocortin receptor subtypes are expressed in the brain?
MC-3 & MC-4
What happens if either MC-3 or MC-4 receptors are deleted?
Obesity in mice becuase no inhibition of food intake signal
Location of NPY and POMC neurones
Paraventricular nucleus (PVN) = satiety
Lateral hypothalamus area / Perifornial area = hunger
What is the Agouti-releated protien?
Neuropeptide that increases appetite = produced in the hypothalamus
What is the mechanism of action of Agouti-related protein?
Expression of AgRP localized to ARC
Acts as antagoinst to MC3 & MC4 receptors = causes increased food intake
Is AgRP effect long or short lasting compared to NPY?
Long lasting
What is AgRP co-expressed with?
NPY in ACR neurones
What does CART stand for?
Cocaine and amphetamine regulated transcript
What affect do cocaine and amphetamine have on CART mRNA?
Increase CART mRNA
Anorexigenic = inhibit food intake
What is CART co-expressed with?
α-MSH in ARC POMC neurones
What happens when there is low activity of CART in depression?
Hypothalamic hypoactivity = associated with hyperphagia and weight gain
What is hyperphagia?
Abnormally great desire for food; excessive eating
Where are Second-Order Neurones found in hypothalamus?
PVN = paraventricular nucleus
LHA/PFA
What do the two Second-Order Neurones do?
PVN = inhibits food intake
LHA/PFA = increases food intake
What does PVN also regulate?
Pituitary hormone secretion
Give two examples of hormones from hypothalamus (PVN)
TRH stimulate secretion of TSH & prolactin
Corticotropin-RH stimualtes adrenocorticotropin hormone (ACTH) secretion
What does adrenocorticotropin hormone (ACTH) do?
Stimulates adrenal gland to produce cortisol
Cuases negative energy balance = reduced food intake, increased sympathetic outflow, increased energy expenditure
Name two neurosecretory cells and what they release
Magnocellular neurones = release oxytocin and vasopressin
Parvocellular = release CRH and TRH
Where do magnocellular neurones release from?***
Magnocellular neurons primarily release oxytocin and vasopressin directly into the bloodstream via the posterior pituitary gland
Where do parvocellular neurones release from?
Parvocellular neurons release hormones like CRH and TRH into the hypophyseal portal system, which then carries them to the anterior pituitary gland to stimulate further hormone production
Name two majorpeptidergic neurones in LHA (important in energy homeostasis)
MCH neurone = releases melanin-concentrating hormone (MCH)
Orexin neurone = releases orexins-A/B
Both causes increased food intake
