L12 - Energy Balance Flashcards

1
Q

What were the early studies performed to implicated hypothalamus in energy balance

A

Ealy lessioning stidues

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2
Q

Lesions to the VMN –>

A

Hyperphagia

Over eating and obestity

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3
Q

Lesions to the LH –>

A

Aphagia leading to starvation

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4
Q

What were the conclusions of the lesioning experiments

How does this compare to the modern view

A

Lead to a theory that the hypothalamus contains a feeding centre and a satiety centre

Modern view is that of a mor eintegrated system - complex set of neurons in various nuclei are invovled

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5
Q

Hypothalamus is sensnisitve to ______ signals

What are these

A

Adiposy signals

Leptin and Insulin

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6
Q

What secretes leptin and insulin

A

Fat cells and pancrease

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7
Q

Where does leptin and insulin act at the hypothalmus

A

Arcuate nucelus

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8
Q

How does leptin reach the arcuate nucelus

A

Through TANYCYTES

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9
Q

Secribe the model of hypothalamuc control of hepatic glucose production

A

Leptin sensing neurones in ARC recieve input regarading energy sotres - in response input pathways that increase hepatic vagal tone which increases hepatic insulin sensitivity

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10
Q

The ARC neurones elicit local responses by connecting to

What is the effect of this

How do they do this

A

PVN VMN LH

Feedback to body via hormonal and nerual outputs to control food intake and energy expenditure

Regulating behaivour, autoomic activty nd metabolical rate

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11
Q

How many classes of LepR+ neurones

A

Two

NPY and Pomc neurones

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12
Q

LepR+ means what

A

Have leptin receptor

So are able to respond to leptin

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13
Q

Leptin ______ NPY nuerones

A

Inhibits

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14
Q

Describe NPY function

A

NPY is a neuropeptide (Y) whose action leads coordination of a vast array of activities to stimulate food intake and reduce energy expenditure

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15
Q

Leptin __________ Pomc neurones

A

Stimulates

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16
Q

Describe pomc function

A

POmc neurohormone.

Reduce food intake and increase energy expendityre

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17
Q

When are leptin levels high

A

When dont need any more food

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18
Q

Two adiposity signals _____________ produced in periphery and travel via ______________ to influence neurones in the ___________

A

Leptin and insulin
ME and tanycytes
Arcuate nucelus

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19
Q

NPY arcuated neurones ______________ and are ________________ inhibited by ______________

A

Synthesise and release
Neuropeptide Y
Inhibited by adipositry signals

20
Q

Pomc arcute neurones sythnesise and release _______________________

A

a-melanocyte-stimulating-hormone (a-MSH)

21
Q

NPY (NPY/AgRP) neurones inhibit the _______ and stimulate the _________

A

INIHIBT PVN

STIMULATE LHA

22
Q

Pomc (a-MSH/CART) stimulates the _________ and inhibits the _____________

A

PVN

LHA (inhibit)

23
Q

PVN has net _________

Causes the release of —— (2)

The net effect is …

A

Catabolic action

Release oxytocin and CRH

Decreases food intake and increases energy expenditure

24
Q

LHA has net __________

Causes the release of ………. (2)

The net effect is …… (2)

A

Anabolic action

Releases orexinA and melanin-concentrating hormone (MCH)

Stimulate food intake and decrease energy expenditure

25
The paper used in the lecture aimed to ...
Understand the genetic program the establishes the neuronal melanocortingergic phenotype and maintains and fully functional neuronal POMC phenotype
26
title of paper used in lecture
Islet 1 specifies the identity of hypothalamic melanocortin neurones and is critical for normal food intake and adiposity in adulthood
27
Transcription factor Islet1 __________________
Predicts and prefigures expression of pomc (ACTH)
28
How was it concluded that islet1 predicts and prefigures expression of pomc (ACTH)
IHC | Combination of IHC and transgenic reporter line (pomc-EGFP) in the adult
29
Islet two binds
To critical homeodomain binding motifs present in the neuronal Pomc enhancers nPE1 and nPE2
30
How did they study the binding of Isl1
Mutate sequences with nPE1 and nPE2 show isl1 no longer recognises mutated DNA and no longer binds
31
So ___- and _____ needed for activity of ___________
nPE1 and nPE2 | Pomc transcription
32
What are the two binding motifs in pomc GENE
nPE1 | nPE2
33
Mutations of nPE1 and nPE2 completely _________________ How was this studied
Prevents the ability of these enahners to drive reported gene expression to hypothalamic pomc neurons in transgenic animals Reporter line - pomc driving expression of EGFP
34
How would you determine if Isl1 required for pomc neurons
Isl1 required for formation of many other other structures ealrier SO need to use a conditonal KO
35
How was the conditional KO made
Mouse 1 - CreERT Mouse 2 - Isl1/LoxP mouse Add tamoxifen at any stage in life to recombine out Exon2 and coditonaly KO ISl1
36
What was seeen in the conditional KO for Isl1
Pomc neurones fail to differentiate
37
Why would you need to analyse expression of both Isl1 and ACTH by immunohistochemistry
To make sure that KO of exon 2 resulted in the absence of Isl1 protein
38
What is the phenotypic effect of KO Isl1
No Pomc Leads to early onset obesity ... Pomc a neurohormone -- reduce food intake
39
What is the model fo rthe development of the hypothalamus Describe it
Sequential anisotropic growth model of hypothalamic development Anterior and mammary regions grow seqentially and in opposite direction from centrally retained FGF10+ pHyp cels
40
Islet1 progenitors differentiate from
Anterior progenitors
41
Isl1+ progenitors give rise to pomc neurones derive from
FGF10+ 'stem' pool
42
FGF10+ cells are retained in _______ as ________
Adulthood | Radial glial cells called tanycytes
43
What is special about some of the FGF10+ tanycytes
Some retain their stem cell actiivity and can give rise to Arc neurones throughout life
44
Potentially throughout life Arc neurones are generated from
Hypothalamic stem cells
45
What is the imolication of the stem cell theory with the idea that glucose requirements can chancge considerably throguhiut life
Pomc and NPY neurones can be generated from hypithalamic stem cells throughout life to anticipate of respond to changes ALLOSTASIS
46
What is the working hypothesis regarding hypothalamic stem cells
Stem cells are stimulated by metabolites/horomones provided by components of the hypothalamic niche and can respond by giving rise to new neurones