Central Regulation Of Food Intake Flashcards

1
Q

Things causing energy expenditure

A

. Resting metabolic rate (sleeping rate and arousal rate)
. Thermic effect of food (digestion/absorption/metabolism, SNS/hormones/neuropeptides)
. Physical activity: (non-exercise activity thermogenesis like SNS and food composition and sports-like exercise)

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2
Q

Food intake is primarily regulated by what brain areas ?

A

. Hypothalamic nuclei: lat. hypothalamus (feeding), ventromedial hypothalamus (satiety), median eminence (circumventricular organ)
. Dorsal vagal complex of brainstem: area postrema, NTS, dorsal motor nucleus of vagus (DMN)

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3
Q

Arcuate nucleus

A

. In ventromedial hypothalamus
. Contains POMC/CART neurons and NPY/AgRP neurons
. Modulate food intake and energy expenditure

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4
Q

POMC/CART neurons

A

. Anorexigenic
. NT: alpha-MSH
. Receptor: MC4R
. Endocrine and autonomic output from paraventricular nucleus second order neurons: TRH and CRH to inc. energy expenditure

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5
Q

NPY/AgRP neurons

A

. Orexigenic
. NT: NPY
. Receptor: Y1 or Y5
. Behavioral output from LH second order neurons: MCH and orexin to inc. food intake

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6
Q

Dorsal vagal complex

A

. Modulate vagal afferent input to DVC
. Peripheral hormones released in response to ingested nutrients activate receptors on vagal afferents located w.in target organ
. Gastric distension activated mechanosensitive vagal afferents and hepatic portal vein glucose and FA activate chemosensitive vagal afferents
. Activate receptors in AP and hormones are released in response to ingested nutrients

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7
Q

Leptin

A

. Synthesized and secreted by white adipocytes
. Concentration in plasma is directly proportional to fat mass
. Stimulates POMC/CART neurons and inhibits NPY/AgRP neurons
. Dec food intake and enhance energy expenditure
. Activated receptors in DVC to dec. food intake

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8
Q

Insulin

A

. Synthesized by pancreatic beta cells
. Stimulated by high glucose
. Activated hypothalamic receptors to dec. food intake and body weight

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9
Q

Ghrelin

A

. Orexigenic systemic hormone that promotes hunger
. Synthesized by gastric P/D1 endocrine cells
. Plasma conc. Is highest immediately fore eating
. Inversely proportional to body weight
. Inc. food intake by activating GHSE on/in DVC, NPY/AgRP neurons, and vagal afferent nn. W/in stomach

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10
Q

Short term anorexigenic signals to regulate satiation/satiety

A

. Intestinal mucosa: nutrients activate receptors on endocrine cells to enhance secretion of substances to promote satiety
. Pancreas Amylin and pancreatic polypeptide
. Glucose

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11
Q

CCK promoting satiety

A

. Activated CCK-1 (CCK-A) receptors in NTS and AP and vagal afferents to promote satiation
. Promotes retention of gastric contents by constricting pyloric sphincter

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12
Q

GLP-1

A

. Peptide secreted from endocrine L cells in ileum and colon in response to glucose or FFA from dietary triglycerides or FFA from colonic bacterial metabolism of carbs
. Potentiation glucose-stimulated insulin secretion
. Activated GLP-1R receptors in NTS and on vagal afferents to dec. food intake

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13
Q

PYY

A

. Peptide secreted from endocrine L cells in ileum and colon in response to FAs, dietary fibers, and bile
. Activates Y2 receptors in DVC, on vagal afferent nn., and on NPY/AgRP neurons to promote satiety
. Inhibits gastric emptying

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14
Q

Serotonin (5-HT)

A

. AA derivative released from endocrine enterochromaffin (EC) or K cells in GI mucosa
. Activated 5-HT3R on POMC/CART neurons, vagal afferent n. Terminals to dec. food intake

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15
Q

Amylin (IAPP)

A

. Co-secreted from beta cells w/ insulin

. Reduces food intake and body weight by actions in brainstem and CNS

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16
Q

Pancreatic polypeptide (PP)

A

. Secreted from endocrine F cells of pancreas

. Activates CNS Y4 receptors to promote satiety and satiation

17
Q

How glucose promotes satiety

A

. Activity of POMC/CART neurons related to plasma glucose
. Activity of orexin neurons indirectly related to plasma glucose
. Activate vagal chemosensitive afferents innervating hepatic portal vein

18
Q

Spatial synergism

A

. Normal exposure of nutrients to mouth to stomach to small intestine
. Meal size can be controlled by sequential activation of pregastric, gastric, and then intestinal stimuli

19
Q

Mechanistic synergism

A

. Combo of more than one individual method to promote satiety and/or satiation
. Visceral vagal afferents and gut peptides
. Gut peptides and other gut peptides
. Gut peptides w/ monoamines
. Bother peripheral and central mechanisms may be involved

20
Q

Nutrient sensing mechanisms

A

. Nutrient does not enter cell but interacts w/ apical plasma membrane receptor
. Intracellular signal transduction results in elevation in intracellular Ca
. Exocytosis of substance by cell (hormone, paracrine, amine)

21
Q

Nutrient sensors

A

. G coupled protein receptors
. Taste receptors
. Ca sensing receptors

22
Q

Nutrient absorption mechanism

A

. Nutrient enters cell by transporter
. Nutrient exits cell via transporter
. Nutrient travels to liver via portal vein

23
Q

Rare monogenic causes of obesity

A

. Leptin gene or receptor mutation
. Prohormone convertase 1 mutation (pro-opiomelanocortin neurons can’t produce alphaMSH)
. Pro-opiomelanocortin gene mutation: neurons can’t synthesize pro-opiomelanocortin)
. Melanocortin 4 receptor mutation (NTs can’t bind to MC4R receptor, 6% massive obesity)

24
Q

Rare obesity syndromes due to chromosomal rearrangements

A

. Prader-willi: 15q11.2-q12 is absent

. SIMI gene mutation: transcription factor involved in formation of paraventricular and supraoptic nuclei

25
Q

Leptin in obesity

A

. Inc. plasma leptin
. Leptin receptor resistance
. Dec. central leptin sensitivity

26
Q

Ghrelin in obesity

A

. Higher density of ghrelin-positive cells in antral mucosa
. Secretion not suppressed w/ food intake
. Secretion not inc. prior to food intake
. Inc. sensitivity to ghrelin

27
Q

CCK levels in obesity

A

Normal post prandial levels

28
Q

PYY levels in obesity

A

. Low post-prandial levels

. Still effective though

29
Q

Gut microbiome in obesity

A

. Enriched in genes coding for enzymes that metabolize indigestible carbs

30
Q

GLP-1 in obesity

A

. Lower post-prandial levels

. Exogenous GLP-1 still effective in obesity