Central Regulation Of Food Intake Flashcards
Things causing energy expenditure
. 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)
Food intake is primarily regulated by what brain areas ?
. 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)
Arcuate nucleus
. In ventromedial hypothalamus
. Contains POMC/CART neurons and NPY/AgRP neurons
. Modulate food intake and energy expenditure
POMC/CART neurons
. Anorexigenic
. NT: alpha-MSH
. Receptor: MC4R
. Endocrine and autonomic output from paraventricular nucleus second order neurons: TRH and CRH to inc. energy expenditure
NPY/AgRP neurons
. Orexigenic
. NT: NPY
. Receptor: Y1 or Y5
. Behavioral output from LH second order neurons: MCH and orexin to inc. food intake
Dorsal vagal complex
. 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
Leptin
. 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
Insulin
. Synthesized by pancreatic beta cells
. Stimulated by high glucose
. Activated hypothalamic receptors to dec. food intake and body weight
Ghrelin
. 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
Short term anorexigenic signals to regulate satiation/satiety
. Intestinal mucosa: nutrients activate receptors on endocrine cells to enhance secretion of substances to promote satiety
. Pancreas Amylin and pancreatic polypeptide
. Glucose
CCK promoting satiety
. 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
GLP-1
. 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
PYY
. 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
Serotonin (5-HT)
. 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
Amylin (IAPP)
. Co-secreted from beta cells w/ insulin
. Reduces food intake and body weight by actions in brainstem and CNS
Pancreatic polypeptide (PP)
. Secreted from endocrine F cells of pancreas
. Activates CNS Y4 receptors to promote satiety and satiation
How glucose promotes satiety
. 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
Spatial synergism
. 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
Mechanistic synergism
. 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
Nutrient sensing mechanisms
. 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)
Nutrient sensors
. G coupled protein receptors
. Taste receptors
. Ca sensing receptors
Nutrient absorption mechanism
. Nutrient enters cell by transporter
. Nutrient exits cell via transporter
. Nutrient travels to liver via portal vein
Rare monogenic causes of obesity
. 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)
Rare obesity syndromes due to chromosomal rearrangements
. Prader-willi: 15q11.2-q12 is absent
. SIMI gene mutation: transcription factor involved in formation of paraventricular and supraoptic nuclei
Leptin in obesity
. Inc. plasma leptin
. Leptin receptor resistance
. Dec. central leptin sensitivity
Ghrelin in obesity
. 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
CCK levels in obesity
Normal post prandial levels
PYY levels in obesity
. Low post-prandial levels
. Still effective though
Gut microbiome in obesity
. Enriched in genes coding for enzymes that metabolize indigestible carbs
GLP-1 in obesity
. Lower post-prandial levels
. Exogenous GLP-1 still effective in obesity
