LT2 Hypothalamus

Question 1

Why is it not just genectic mutation/drift that is causing the rapid increase in obesity rates?

Answer 1

Because the timeframe is too quick for it to be caused by genes alone

Question 2

What is the % of heritability of fat mass?

Answer 2

40% to 70%

Question 3

Give an example of one monogenetic mutation that causes obesity

Answer 3

Leptin and leptin receptor mutation

Question 4

Define polygenic aetiology

Answer 4

A characteristic that is influence by two or more genes

Question 5

What are our survival genes likely to do?

Answer 5

Drive obesity

Question 6

Why are our survival genes likely driving obesity?***

Question 7

Why is it difficult to lose weight, once gained?

Answer 7

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

Question 8

CNS influence energy balance and body weight by what 3 mechanisms?

Answer 8

Behaviour = feeding and physical activity

ANS activity = regulates energy expenditure

Neuroendocrine system = secretion of hormones

Question 9

Why is obesity a disease of the brain?

Answer 9

CNS controls energy intake and body weight

Brain integrates signals

Question 10

What is the main CNS centre responsible for energy intake control?

Answer 10

Hypothalamus

Question 11

What is the satiety centre in hypothalamus?

Answer 11

Ventromedial hypothalamus

Question 12

What is the hunger centre in hypothalamus?

Answer 12

Lateral hypothalamus

Question 13

What happens when ventromedial hypothalamus is removed?

Answer 13

Causes obesity because satiety signals not received

Question 14

What happens when lateral hypothalamus is removed?

Answer 14

Causes leanness because hunger signals are not received

Question 15

Why is an individuals weight stable over lengthy periods of time?

Answer 15

Because energy balance is controllled by feedback loops

They act to maintain constancy of total body energy stores

Question 16

Why do most people regain weight after stopping dieting?

Answer 16

Because of the feedback loops bringing the body back to usual weight

Question 18

How is food intake and energy expenditure modulated? (flowchart)

Answer 18

Signals produced in response to body energy status

Sensed by the brain

Signals in brain act to modulate food intake and energy expenditure

Question 19

Where is the hypothalamus located?

Answer 19

At the base of the brain, in the diencephalon

Attached above the pituitary gland

Question 20

Define sagittal section

Answer 20

Vertical slice through the body

Divides it into left and right sides

Question 21

Name the 6 areas of the hypothalamus

Answer 21

Arcuate nucleus (ARC)

Ventromedial nucleus (VMN)

Dorsomedial nucleus (DMN)

LHA/PFA = lateral hypothalamus / perifornical area

Paraventricular nucleus (PVN)

Question 22

What is the central role of ARC?***

Answer 22

Nutrient homeostasis = integrate signals

Required for optimal functioning of organism

Question 23

Define First-Order Neurones

Answer 23

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

Question 24

Define Second-Order Neurones

Answer 24

Interneurons = that relay sensory information from the spinal cord/brainstem to the thalamus and cerebellum

Question 25

Glutamate (agonist, area effected, effect, half-life)

Answer 25

NMDA LHA Stimulates feeding Lasts less than 10mins = short lasting action

Question 26

GABA (agonist, area effected, effect, half-life)

Answer 26

Muscimol (GABA_A receptor agonist) VMN, DMN, or PVN Stimulates feeding Lasts about 30mins

Question 27

Opioids (agonist, area effected, effect, half-life)

Answer 27

B-endorphin, dynophin, long-acting enkelphalin ARC, VMN, DMN, or PVN Stimulates feeding Effects short-lived and modest

Question 28

Monoamines (agonist, area effected, effect, half-life)

Answer 28

Noradrenaline, dopamine, serotonin SUPRESS food intake

Question 29

What system are many anti-obesity drugs developed to act on?

Answer 29

Monoamin system

Question 30

Why are most anti-obesity drugs withdrawn?

Answer 30

Side effects

Question 31

Name the neurotransmitters that stimulate feeding and the one that supresses it

Answer 31

Glutamate, GABA, Opioids = stimulate Monoamins = supress

Question 32

What is the name for something that increases appetite or food intake and its opposite word

Answer 32

(AN) OREXIGENIC

Question 33

Name the orexigenic neuropeptides

Answer 33

NPY, MCH, Agouti Galanin, Orexins, Ghrelin, Endocannabinoids

Question 34

Name the anorexigenic neuropeptides

Answer 34

α-MSH, CART, GLP-1, TRH, CRH, PYY Leptin & Insulin (both hormones not neuropeptides)

Question 35

What 3 things does neuropeptide Y do?

Answer 35

When injected into hypothalamus = stimulates food intake, reduces energy expenditure and induces lipogenic enzymes in fat and liver cells

Question 36

Where are neuropeptide Y-containing neurones mainly found?

Answer 36

ARC and DMN

Question 37

What happens with repeated administraiton of NPY to hypothalamus?

Answer 37

Leads to obesity = because stimulates food intake, reduces energy expenditure and incduces lipogenic enzymes

Question 38

When is NPY gene expression increased?

Answer 38

After fasting or reduce feeding

Question 39

What are NB mice? And what happens when they lack NPY receptor subtypes?***

Answer 39

These mice lack Y1 or Y5 receptor subtypes. They are pre-disposed to mild obesity because of functional redundancy and developmental copmensation

Question 40

What does α-MSH stand for?

Answer 40

α-melanocyte stimulating hormone

Question 41

What is α-MSH?

Answer 41

Non-opioid peptide

Question 42

What does POMC gene encode?

Answer 42

α-melanocyte stimulating hormone

Question 43

What is the role of α-MSH?

Answer 43

Acts in the ARC of hypothalamus = INHIBITS food intake

Question 44

When is POMC gene expression reduced and increased?

Answer 44

Decreased after fasting Increased after increase in energy balance Because codes for α-MSH, which inhibits food intake

Question 45

What melanocortin receptor subtypes are expressed in the brain?

Answer 45

MC-3 & MC-4

Question 46

What happens if either MC-3 or MC-4 receptors are deleted?

Answer 46

Obesity in mice becuase no inhibition of food intake signal

Question 47

Location of NPY and POMC neurones

Answer 47

Paraventricular nucleus (PVN) = satiety Lateral hypothalamus area / Perifornial area = hunger

Question 48

What is the Agouti-releated protien?

Answer 48

Neuropeptide that increases appetite = produced in the hypothalamus

Question 49

What is the mechanism of action of Agouti-related protein?

Answer 49

Expression of AgRP localized to ARC Acts as antagoinst to MC3 & MC4 receptors = causes increased food intake

Question 50

Is AgRP effect long or short lasting compared to NPY?

Answer 50

Long lasting

Question 51

What is AgRP co-expressed with?

Answer 51

NPY in ACR neurones

Question 52

What does CART stand for?

Answer 52

Cocaine and amphetamine regulated transcript

Question 53

What affect do cocaine and amphetamine have on CART mRNA?

Answer 53

Increase CART mRNA Anorexigenic = inhibit food intake

Question 54

What is CART co-expressed with?

Answer 54

α-MSH in ARC POMC neurones

Question 55

What happens when there is low activity of CART in depression?

Answer 55

Hypothalamic hypoactivity = associated with hyperphagia and weight gain

Question 56

What is hyperphagia?

Answer 56

Abnormally great desire for food; excessive eating

Question 57

Where are Second-Order Neurones found in hypothalamus?

Answer 57

PVN = paraventricular nucleus LHA/PFA

Question 58

What do the two Second-Order Neurones do?

Answer 58

PVN = inhibits food intake LHA/PFA = increases food intake

Question 59

What does PVN also regulate?

Answer 59

Pituitary hormone secretion

Question 60

Give two examples of hormones from hypothalamus (PVN)

Answer 60

TRH stimulate secretion of TSH & prolactin Corticotropin-RH stimualtes adrenocorticotropin hormone (ACTH) secretion

Question 61

What does adrenocorticotropin hormone (ACTH) do?

Answer 61

Stimulates adrenal gland to produce cortisol Cuases negative energy balance = reduced food intake, increased sympathetic outflow, increased energy expenditure

Question 62

Name two neurosecretory cells and what they release

Answer 62

Magnocellular neurones = release oxytocin and vasopressin Parvocellular = release CRH and TRH

Question 63

Where do magnocellular neurones release from?***

Answer 63

Magnocellular neurons primarily release oxytocin and vasopressin directly into the bloodstream via the posterior pituitary gland

Question 64

Where do parvocellular neurones release from?

Answer 64

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

Question 65

Name two majorpeptidergic neurones in LHA (important in energy homeostasis)

Answer 65

MCH neurone = releases melanin-concentrating hormone (MCH) Orexin neurone = releases orexins-A/B Both causes increased food intake