Flashcards in Food Intake Deck (23)
Breakdown of glycogen in muscle and liver (important for fight or flight to get quick energy)
Synthesis of glucose from prevursors in liver
Metabolism of glucose to produce ATP
Production of fat induced by insulin
Breakdown of fat induced by glucagon, epinephrine and GH
What is the function of ghrelin in regulation of food intake?
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...)
What is the function of insulin in regulation of food intake?
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
What is the function of Leptin in regulation of food intake? Experiment to show its function?
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.
What is the function of Agouti-related peptide (AGRP) in regulating good intake?
1. Angagonist of MC3R and MC4R receptors (they work to DECREASE food intake)
2. Orexigenic (stimulates hunger)
3. Down-regulated by Leptin
What is the function of endocannabinoids in regulating food intake?
1. Orexigenic (promote hunger, munchies)
2. Down-regulated by Leptin
What is the function of Leptin/Insulin and ghrelin in the reward pathway of food?
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
What is the effect of a high calorie diet on the reward pathway?
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)
What is the mechanism of food acting as a reward?
Sucrose increases striatal dopamine release, so dopamine goes up
What is the experimental evidence that stress affects food intake?
Stress exposure in mice (restrain for 3 days) attenuates body food intake and has lasting effects on body weight.
What effects does chronic CRH exposure have on food intake?
1. Increases gluconeogenesis
2. Induces Insulin resistance
3. Fat depots redistributed to abdominal regions
4. Preference to consume high calorie food (comfort food)
What hormone is responsible for the stress-caused change in food intake?
Corticotropin-releasing factor (CRH/CRF)
sources of glucose
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
adipose tissue and metabolic energy
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
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
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
D2R - neuroadaptation to cocaine/comfort food/chronic stress
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
social status and emotional feeding
subordinates prefers high calorie food;
antagonism of CRH type 1 receptors reduces emotional feeding in subordinates