Regulation of Food Intake Flashcards
Arcuate nucleus anorexigenic pathway
a-melanocortin (a-MSH) released by pro-opiomelanocortin POMC neurons
Binds to MCR-4 present in second-order neurons
Signaled by insulin, leptin, CCK
Inhibits PVN, LHA and DMN
Arcuate nucleus orexigenic pathway
Neuropeptide Y NPY - hunger signals stimulate release
Binds Y1R
Agouti-related peptide AGRP is also released which is a antagonist of MCR-4 of anorexigenic pathway
Signaled by Ghrelin
Activates VMN, DMN, LHA and PVN
Leptin or leptin receptor gene deficiency causes
Early onset severe obesity, infertility, hyperphagia, infections
MCR4 mutation
Early onset severe obesity
Increased linear growth
Hyperphagia, hyperinsulinemia
Most common genetic cause of obesity
Prader-Willi syndrome
Slow infant growth Small hands and feet Mental retardation Hypogonadism Hyperphagia leading to severe obesity *Paradoxically elevated ghrelin
POMC deficiency
Obesity Red hair Adrenal insufficiency due to ACTH deficiency Hyperproinsulinemia Cholestatic jaundice
Vagal–>NTS–>hypothalamus circuit and satiety
Several peptides that stimulate satiety and decrease feeding activate receptors on vagal afferents
If vagal activity is blocked, the amount of material in the stomach no longer influences meal size
*CCK acts on vagal afferents to activate them and cause satiety
NTS
NTS (nucleus tractus solitaries) is crucial in the interpretation and relaying of peripheral signals
Vagal signals received by NTS is integrated with hypothalamic information to produce appropriate feeding behavior and metabolic response
Lateral hypothalamic area LHA
Hunger center
Neurons project throughout brain and release orexigenic peptides MCH (melanin concentrating hormone) or orexins A/B
LHA is glucose sensitive
Ventromedial hypothalamic nucleus VMN
Satiety center - glucose sensitive
Paraventricular nucleus PVN
Contains neurons that in turn project to both cerebral cortex and areas of brainstem
Insulin effect on NPY/POMC
Inhibits NPY stimulates POMC
PYY
Released by L cells of ileum and colon following meals
Binds to Y2R in hypothalamus
Inhibits NPY neurons
Releases inhibition of POMC neurons
Leptin
Released by cells in adipose tissue
Inhibits NPY pathway
Stimulates POMC pathway
Suppresses appetite, increases metabolism, decreases ghrelin
Leptin and obesity
In obese children w/congenital leptin deficiency, subq recombinant leptin reduces fat mass, hyperinsulinemia and hyperlipidemia
However, obesity in humans (due to diet etc..) is often associated with high leptin levels and failure to respond to exogenous leptin (leptin resistance)
GLP-1
Co-secreted with PYY from L cells in intestine
Incretin
Levels rise after meal and fall during fasting
Reduces food intake, suppresses glucagon secretion and delays gastric emptying
Oxyntomodulin
Proglucagon derived peptide
Released from L cells in the intestine in response to ingested food and in proportion to caloric intake
Anorectic effect
Pancreatic peptide
Released from pancreatic islet of Langerhans cells
Putatively, decreases food intake directly through Y4R in brainstem and hypothalamus
May also act via the vagus nerve to produce anorectic effects
Amylin
Stored and released with insulin in response to food intake Anorectic effects (inhibition of NPY release)
Anorexia nervosa
Polymorphisms in genes involved in eating attitudes, regulation of eating behavior, motivation and reward mechanisms
Basal and pulsatile secretion of leptin is reduced in association with reductions in fat mass
Ghrelin resistance appears to be a conducive factor to a restrictive diet
Elevated levels of PYY - might contribute to decreased nutrient intake and disordered eating psychopathology
