Food Intake

Question 1

Define glycogenolysis

Answer 1

Breakdown of glycogen in muscle and liver (important for fight or flight to get quick energy)

Question 2

Define gluconeogenesis

Answer 2

Synthesis of glucose from prevursors in liver

Question 3

Define glycolysis

Answer 3

Metabolism of glucose to produce ATP

Question 4

Define lipogenesis

Answer 4

Production of fat induced by insulin

Question 5

Define lipolysis

Answer 5

Breakdown of fat induced by glucagon, epinephrine and GH

Question 6

What is the function of ghrelin in regulation of food intake?

Answer 6

1. expressed by stomach cells and to a lesser extent the ARC
2. Ghrelin is increased in circulation during the inter-meal interval and acts to initiate food intake
3. binds its receptor in the ARC to stimulate the expression of NPY and AGRP
4. regulation of ghrelin (check the slide, tedious…)

Question 7

What is the function of insulin in regulation of food intake?

Answer 7

1. secreted by pancreatic beta cells in response to a meal
2. stimulates leptin synthesis and release by adipocytes
3. crosses BBB to bind to the insulin receptor substrate 1 and 2 in ARC
4. peripheral insulin resistance - type II diabetes
5. for leptin and insulin just remember these up regulate alphaMSH and down regulate NPY

Question 8

What is the function of Leptin in regulation of food intake? Experiment to show its function?

Answer 8

1. synthesized and secreted by adipocytes showing a 24 hour rhythm entrained to postprandial insulin;
2. cross the BBB to bind to receptors in ARC, but in obesity, leptin does not cross BBB
3. Appetite inhibitor. Leptin down regulates NPY expression in ARC to inhibit feeding (NPY is a potent orexigenic neuropeptide)
4. leptin down regulates AGRP expression in the ARC to inhibit feeding (AGRP coexpressed in NPY neurons)
5. leptin targets endocannabinoids (receptors CB1 and CB2 for these ligand are located in reward and feeding pathway; endocannabinoid expression in the hypothalamus is down regulated by leptin)
6. Leptin targets POMC
   stimulates POMC expression in the ARC in neurons;
   one product of POMC is alpha-MSH;
   alpha-MSH is an agonist of the MC3/4-R in PVN/VMH that reduces food intake.

Question 9

What is the function of Agouti-related peptide (AGRP) in regulating good intake?

Answer 9

1. Angagonist of MC3R and MC4R receptors (they work to DECREASE food intake)
2. Orexigenic (stimulates hunger)
3. Down-regulated by Leptin

Question 10

What is the function of endocannabinoids in regulating food intake?

Answer 10

1. Orexigenic (promote hunger, munchies)

2. Down-regulated by Leptin

Question 11

What is the function of Leptin/Insulin and ghrelin in the reward pathway of food?

Answer 11

Leptin + Insulin attenuate the reward response so the positive feel-good dopaminergic response to sucrose is decreased; coexpressed in the TH neurons (enzyme responsible for DA synthesis)

administration of ghrelin to the VTA increases preference for highly palatable foods and induce DA overflow in the NAc

Question 12

What is the effect of a high calorie diet on the reward pathway?

Answer 12

1. HCD mice are chunkier than normal which makes sense.
2. HCD mice have DECREASED dopamine receptor expression
3. Decreased D2R expression > worked harder to get more food
4. In people, increased BMI is correlated with downregulated D2R expression (so they eat more tocompensate)

Question 13

What is the mechanism of food acting as a reward?

Answer 13

Sucrose increases striatal dopamine release, so dopamine goes up

Question 14

What is the experimental evidence that stress affects food intake?

Answer 14

Stress exposure in mice (restrain for 3 days) attenuates body food intake and has lasting effects on body weight.

Question 15

What effects does chronic CRH exposure have on food intake?

Answer 15

1. Increases gluconeogenesis
2. Induces Insulin resistance
3. Fat depots redistributed to abdominal regions
4. Preference to consume high calorie food (comfort food)

Question 16

What hormone is responsible for the stress-caused change in food intake?

Answer 16

Corticotropin-releasing factor (CRH/CRF)

Question 17

sources of glucose

Answer 17

1. intestinal absorption from diet
2. endogenous generation of glucose primarily by liver - glycogenolysis and gluconeogenesis
3. glycolysis: metabolism of glucose
   production of ATP
   production of precursors used for other cellular processes

Question 18

adipose tissue and metabolic energy

Answer 18

1. major source of energy stores
2. lipogenesis is the production of fat induced by insulin
3. lipolysis is the breakdown of fat induced by glucagon, epinephrine, and is inhibited by insulin

Question 19

the NTS

Answer 19

nucleus of solitary tract (NTS)
cluster of neurons embedded in medulla;
receives visceral afferents information by the vagus in response to gut distension and gut peptides to limit meal size;
sends projection to limbic and hypothalamic areas

main point: signal from stomach and intestine up/down regulates food intake in brain through NTS and ARC

Question 20

glucose sensors

Answer 20

1. neurons in the ARC and PVN respond to signals from glucose metabolism that, in turn, affects feeding behavior
2. more ATP to AMP results in release POMC-derived peptides, notably alpha-MSH that attenuates food intake
3. more AMP to ATP results in increase glucose uptake and fatty acid oxidation as well as the release NPY and AGRP that stimulates food intake

Question 21

D2R - neuroadaptation to cocaine/comfort food/chronic stress

Answer 21

decrease in D2R availability and decrease of cocaine self-administration;

D2R KO resulted in increase reward thresholds when given access to high caloric but not chow diet

signals from the stress axis target DA neurons in mesolimbic regions producing a dysregulation of DA neurotransmission

Question 22

social status and emotional feeding

Answer 22

subordinates prefers high calorie food;

antagonism of CRH type 1 receptors reduces emotional feeding in subordinates

Question 23

obesity and hippocampal function

Answer 23

1. slower learning
2. reduced long term potentiation
3. reduced Hp spine density