When things go wrong part 1

Question 1

Energy sources for body & brain

Answer 1

1 - glucose
2 - glycogen
3 - Lipids

Question 2

Detection system

Answer 2

• recognise deviation from set point
• alter physiology or behaviour to correct imbalance
• recognize when correction has been effective
  (Does not apply to the long-term regulation of energy stores& feeding)

Question 3

Glucostatic Hypothesis

Answer 3

• Brain monitors circulating blood glucose levels
• when they fall below a critical level, we become hungry
• after we eat & blood glucose levels return to normal - no longer hungry
  BUT –> diabetics have high levels of glucose, always hungry without insulin

Question 4

Lipostatic Hypothesis

Answer 4

• Brain monitors body fat stores
• If they fall below a critical level - makes us hungry
• After we’ve eaten & replaced missing body fat, not hungry anymore
  BUT - get hungry ~ 4hrs after a meal - not lost any weight

Question 5

Bottom-up modulation

Answer 5

Ascending modulatory influences determine the level of incentive salience directed to specific nutrients

Question 6

CNS regulation of energy homeostasis

Answer 6

CNS integrates input from long-term energy stores (e.g. leptin) & short-term meal-related signals (nutrients & gut-derived satiety signals) to regulate food intake & EE that is able to maintain stable body fat stores over time

Question 7

Functions of the hypothalamus

Answer 7

1 - regulation of food intake
2 - autonomic regulatory center (influences HR, BP, respiratory rate, GI mobility, pupillary diameter)
3 - regulation of thirst & water balance
4 - regulation of body T
5 - regulation of sleep wake cycle
6 - emotional responses 
7 - hormonal control

Question 8

Which structures does the hypothalamus influence secretion from in regulatin energy balance & metabolism?

Answer 8

1 - Thyroid gland
2 - Adrenal gland
3 - Pancreatic islet cells

Question 9

Orexigenic substance

Answer 9

any substance that stimulates feeding behaviour

Question 10

Anorexigenic substance

Answer 10

Any substance that inhibits feeding behaviour

Question 11

AgRP/NPY Neurons

Answer 11

AgRP/NPY neuons express ghrelin receptors - detect ghrelin to facilitate energy intake (hunger-related metabolic molecule)

Question 12

POMC neurons

Answer 12

POMC neurons express leptin or insulin receptors - respond to anorexigenic substances: adipose-originated leptin or pancreas-derived insulin

Question 13

T/F POMC neurons expressing leptin receptors co-produce insulin receptors

Answer 13

False - POMC neurons expressing leptin receptors do not co-produce insulin receptors (& vice versa) indicating existence of heterogeneous subtypes of POMC neurons in hypothalamus

Question 14

Dominant melanocortin receptors

Answer 14

MC3/4R

Question 15

Arcuate Nucleus function

Answer 15

Integrates info for blood glucose & body fat levels

Question 16

What are the 2 subtypes of arcuate nucleus neurons?

Answer 16

NPY & AgRP expressing neurons

POMC & CART expressign neurons

Question 17

What does activation of NPY/AgRP neurons result in?

Answer 17

Increases food intake & decreases EE

Question 18

What does activation of POMC neurons result in?

Answer 18

Decreases food intake increases EE

Question 19

Short-term vs Long-term regulation of food intake

Answer 19

Short term regulation:
Preventing overeating at each meal
Long term regulation:
maintenance of normal quantities of energy stores in the body

Question 20

Types of rapid feedback signals during a meal to regulate the amount eaten

Answer 20

1. intestinal stretch receptors

2. Peripheral anorexic hormonal signals

Question 21

Hormones released by lipid & carbohydrates

Answer 21

Lipid - CCK release

Carbohydrates - GLP-1, PYY, Insulin

Question 22

CCK, GLP-1 & PYY role

Answer 22

CCK: released in response to fat entering the duodenum; Stimulates POMC/CART neurons
–> reduces food intake
GLP-1: released in response to carbohydrates in intestine; Stimulates POMC/CART neurons
–> reduces food intake
PYY: stimulated by food intake & released from GI tract; Inhibits the NPY/AgRP neurons
–> reduces food intake

Question 23

Peripheral orexigenic signal

Answer 23

Ghrelin:

stimulates food intake; produced by stomach

Question 24

NPY acts on which receptors in POMC

Answer 24

NPY acts on POMC NPY Y1 receptors -> inhibits POMC neurons

Question 25

Adipokines

Answer 25

``` 1 - leptin 2 - Resistin 3 - Adiponectin 4 - Visfatin 5 - TNF & IL ```

Question 26

Action of leptin

Answer 26

Correlates with adipose tissue mass - increase concentration & resistance in obese individuals Ineffective peripherally in humans

Question 27

Action of resistin

Answer 27

Induced in obesity --> leads to insulin resistance

Question 28

Action of Adiponectin

Answer 28

Insulin sensitizing & anti-inflammatory Suppressed in obese paralleling insulin resistance Increases EE & fatty acid metabolism

Question 29

Action of TNF & IL-6

Answer 29

Promotes low level inflammation in fat & throughout body

Question 30

How does Leptin disinhibit POMC neurons?

Answer 30

- Decreases GABAergic tone on POMC - mediated by AgRP neurons - Inhibits AgRP neurons - Inhibits pre-synaptic GABAergic neurons

Question 31

Selective antagonist on D2 dopamine receptors

Answer 31

Raclopride

Question 32

D2 receptor function

Answer 32

Activate inhibitory G-proteins by inhibiting adenylate cyclase - cAMP formation

Question 33

Increased Raclopride binding in anteroventral striatum in recovered anorexics could be due to:

Answer 33

- Reduction in intrasynaptic DA concentration - Elevation of density of D2/D3 receptors - Increased affinity of D2/D3 receptors in this region

Question 34

More evidence for role of DA in anorexia

Answer 34

1. CSF DA metabolites reduced in malnourished AN patients & persists after recovery 2. AN have impairment in visual discrimination learning - reflects defective DA signaling 3. Anorexics have altered frequency of functional polymorphisms of DA D2 receptor genes - may effect receptor efficiency of receptor transcription & translation

Question 35

Antagonist of H1 receptors

Answer 35

[11C]doxepin

Question 36

When obese individuals restrict energy by dieting:

Answer 36

- > increased sympathetic activity - mobilize fatty acids from adipose stores - > results drop in leptin production that exceeds loss of fat from storage deposits - > reduced leptin - leads decreased muscle & other thermogenic organ sympathetic activity - leads to decreased resting EE - > low leptin levels - disinhibit NPY/AgRP neurons & inhibits POMC/CART neurons - causing a strong drive to seek & ingest food

Question 37

Diet induced weight loss increases baseline levels of :

Answer 37

Ghrelin

Question 38

Surgically induced weight loss (gastric bypass) decreases:

Answer 38

ghrelin + prolonged suppression of ghrelin weight loss possibly due in part to lack of appetite stimulation

Question 39

The leading theory for maintenance of body weight as a result of long-term matching of food intake to EE relates to the:

Answer 39

Amount of fat stored in adipose tissue

Question 40

A defect resulting in a lack of neuropeptide Y in the hypothalamus would likely result in:

Answer 40

Decrease in appetite

Question 41

Leptin decreases the reward value of food by:

Answer 41

- Inhibition of the JAK-STAT pathway - Inhibiting dopaminergic neurons in the ventral tegmental area X - not by activating the JAK-STAT pathway in the ventral tegmental area

Question 42

Peripheral anorexigenic substances act on the arcuate nucleus by:

Answer 42

Stimulating POMC/CART neurons & increasing EE

Question 43

Insulin sensitizing & anti-inflammatory molecule that increases fatty acid metabolism & increases EE. levels decrease in obese individuals

Answer 43

Adiponectin

Question 44

Molecule thought to be one of the main contributors to insulin resistance in obese individuals

Answer 44

Resistin

Question 45

Released in proportion to perceived pleasantness of food

Answer 45

Dopamine

Question 46

This drug is responsible for increased anxiety, sedative effects & increased dysphoria in recovered ANs - response that is opposite to that experienced by healthy individuals

Answer 46

Amphetamine

Question 47

Brain region that shows persistent hypoperfusion in recovered ANs even after weight gain

Answer 47

Anterior Cingulate Cortex (ACC)

Question 48

Reduction in volumes of this brain region results in deficits in perceptual organization & conceptual reasoning in recovered ANs

Answer 48

Right parietal lobe

Question 49

Increased density of these receptors (that bind [11C]doxepin) is thought to increase the vulnerability of women to develop anorexia

Answer 49

Histamine H1 receptors