Hypothalamic pituitary axis 2 Flashcards Preview

BMS1052_ > Hypothalamic pituitary axis 2 > Flashcards

Flashcards in Hypothalamic pituitary axis 2 Deck (30)
Loading flashcards...
1
Q

Determining body weight

belief that is held by most people

A

Energy intake = energy expenditure

2
Q

Energy Expenditure

A

Thermogenesis –> adaptive, variable, Brown Adipose Tissue, regulated by SNS
Physical Activity –> voluntary, variable
Metabolic Rate –> obligatory expended in cell function

3
Q

Frohlich’s Syndrome

A

Concluded that the adiposogenital syndrome seen in patients was due to injury to the pituitary gland (1901)

Aschner demonstrated that removal of the pituitary in dogs did not lead to obesity (1912)

Role of the hypothalamus in regulating food intake - Hetherington and Ranson (1940)

4
Q

The dual centre hypothesis of feeding

experiment with mouse

A

lesion of the lateral hypothalamus —> lateral hypothalamic syndrome —> underweight

Lesion to ventromedial hypothalamus —> ventromedial hypothalamic syndrome —> obesity

5
Q

What is the interaction between the periphery and the brain in setting body weight?
Lipostatic theory

A

The brain monitors the amount
of body fat and acts to “defend”
this energy store against changes

This theory requires there to be a link or a messenger between
body fat and the brain
The much sought after ob gene product which circulates in the blood in proportion to fat mass

6
Q

Coleman’s parabiosis experiment

A

Ob/ob mouse  lacks the Ob gene within its fats

parabiosis of Ob/Ob mouse and the normal mouse –> both mouse normal weight

7
Q

Discovery of Leptin (leptos

A

ob gene normally, expressed in fat cells, was sequenced in the mid 90’s and the product named “leptin”.
Daily ip injections of leptin in mice
reduction of body weight
percentage body fat (12.2% to 0.7% !!)
decrease insulin and glucose
increase in temperature, metabolic rate and activity
a

8
Q

Neuronal circuitry in the hypothalamus activated

by

A

peripheral hormones

9
Q

arcuate nucleus

A

A collection of neurons (nerve cells) in the hypothalamus of the brain. Some arcuate neurons contain dopamine and act to inhibit the release of the hormone prolactin by the pituitary gland. Other arcuate neurons contain a substance called neuropeptide Y (NPY) and influence hunger.

10
Q

which neurons in the hypothalamus promote feeding?

A

NeuropeptideY(NPY) + Agouti Related Peptide (AgRP)= “orexigenic

11
Q

which neurons in the hypothalamus stop feeding?

A

Proopiomelanocortin (POMC) +
Cocaine Amphetamine RegulatedTranscript
(CART) = “anorexigenic”

12
Q

Is leptin orexigenic or anorexigenic?

A

Leptin is an anorexigenic hormone, it inhibits the neurons that promote feeding and excite those neurons that would inhibit feeding
Net result= leptin results in reduction of feeding

13
Q

What happens during starvation ?

A

Responses to decreased levels of leptinie in starvation (reduced body fat leads to reduced leptin levels)

Humoral
In low leptin level the release Hypophysiotropic hormones TRH and CRH are present in the paraventricular nucleus and act in the anterior pituitary to release ACTH and TSH which increase “metabolic rate” is inhibited —>Reduction of expenditure of energy

it stimulate the NPY and AgRP neruons which promote feeding

visceromotor
Not shown here change sympathetic outflow to sites which increase energy expenditure

somatic
Behavioral responses related to food seeking

Which homoeostatically increase our body weight

14
Q

Responses to increased levels of leptinie weight gain

A

Leptin activate the anorexigenic neurons CART and POMC in the arcuate nucleus in the lateral hypothalamus which inhibits feeding

it stimulate the Hypophysiotropic hormones in the paraveticular nucleus which cause the release of TRH and CRH into the anterior pituitary gland which cause the release of ACTH, and TSH which increase the metabolic rate and energy expenditure

15
Q

The role of the hypothalamus- Long term control of energy balance

A

. While short-term weight loss is readily achieved with diet and exercise, most individuals are unable to maintain the weight loss for an extended period. Avoiding weight regain is usually a challenge because physiologic mechanisms, some poorly understood, promote weight regain. Up to 75% of dieters, especially people on very low calorie diets (400-800 kcal/day) regain much of the lost weight within 1 year.22
As weight loss objectives are often not achieved through diet and behaviour modification alone, there remains a need for more efficacious approaches. An extensive study program has shown that Xenical, when used in conjunction with a mildly hypocaloric diet, produces significant weight loss, reduced weight regain, improvements in the comorbidities associated with obesity and an improved quality of life compared with diet alone.

16
Q

ENERGY EXPENDITUR and weight

A

ENERGY EXPENDITURE CAN BE REGULATED IN MAN

10% weight gain–> 10% increased in energy expenditure

17
Q

Why is it difficult to maintain weight loss?

A

It is difficult to maintain weight loss - metabolic adaptation occurs following weight loss

There’s a persistent need that is generated in weight loss t put that weight back on as the BMI decreases significantly  difficult to maintain that weight loss

18
Q

Short term regulation of food intake

A

Ghrelin: feeding promoting hormone
Satiety signals: hormones promoting stop feeding

Ghrelin produced in the stomach and acting on feeding centres (NPY and AgRP neurons)
in the brain builds up prior to a meal and then is reduced following the meal

19
Q

Satiety Signals

A
Gastric distension and cholecystekinin (CCK)
and insulin (produced by pancreases)  acts on the vagus nerve that takes the signal to the nucleus of the solitary tact to produce satiety 

During feeding stomach stretch, the stretch sensitive neurons detect that and send a signal to the brain to the nucleus of the solitary tact to produce satiety

20
Q

How is body weight regulated?

A
Leptin produced by the fat cells 
PYY-3 36 produced by small intestine 
Amylin produced by pancreases
CCK produced by pancrease 
Insulin 
and Ghrelin produced in stomach 
hedonic input 
stretch receptor in Stomach and duodenum 

Ghrelin is an orexigenic hormones
The rest are satiety hormone

21
Q

How do changes in these hormones after weight loss

make it difficult to maintain weight loss

A

The Ghreline hormone level keep increasing after 10 weeks and 62 weeks of diet

and the level of CCK,PYY and Amylin decreases

22
Q

Schematic showing the flow of information amongst distributed neural networks
controlling food intake, energy expenditure and energy homeostasis

A

Orbital frontal cortex is intimately connected with other related areas of cortex including the pre- frontal, anterior cingulate and insula cortex together with the
amygdala and hippocampus form
the “paralimbic cortex” ??

Stored polymodal representations
of experiences with food

23
Q

Hedonistic vs Homeostatic eating

A

Homeostatic feeding is necessary for basic metabolic processes and survival, while hedonic feeding is driven by sensory perception or pleasure.

24
Q

Reward Pathways –

The basis of hedonistic feeding

A

Electrical self stimulation.

Excitation of dopaminergic
neurons arising from the 
ventral tegmental area and 
projecting to the basal 
forebrain
25
Q

The mesolimbic (dopamine) reward pathways

A

The mesolimbic dopamine pathway is thought to play a primary role in the reward system. It connects the ventral tegmental area (VTA), one of the principal dopamine-producing areas in the brain, with the nucleus accumbens, an area found in the ventral striatum that is strongly associated with motivation and reward.

26
Q

There is a division amongst the core processes of reward into

A

‘liking”

“wanting”

27
Q

‘liking

A

“Liking” is an objective affective reaction that is mediated for taste in the brain by distributed neural networks extending from the brain stem to the nucleus accumbens

Examples of hedonic “liking” reactions are stereotypical and preserved across species and exist without higher centres

28
Q

What are the key brain regions and neurotransmitters involved? in liking

A

“Liking” is mediated by mu opioids acting at receptors in the nucleus accumbens (ie local injection
of morphine or the mu opioid receptor agonist DAMGO leads to appetite for highly palatable,
highfat, sweet foods)

selective mu opioid receptor antagonists reduce the “liking” of previously favoured
sweet solutions

29
Q

What are the transmitters involved? wanting

A

Dopamine was originally thought to be the transmitter that mediated sensory
pleasure or “liking” however 6 OH DA lesions (which disrupt dopamine show otherwise
ie elimination of dopamine from the n accumbens and ventral striatum leads to aphagia
(reduced feeding) but no shift in “liking”

increasing levels of dopamine in the n accumbens does not change “liking” but
increases the motivational component of reward or “wanting”. “Wanting” is mediated by dopamine

30
Q

wanting

A

“wanting” is an objective motivational process that is often termed incentive salience