alimentary mechanisms Flashcards
appetite: recall the hormones (hypothalamic, leptin, ghrelin, peptide YY) and neuronal populations (AGrP & POMC) involved in the regulation of appetite and explain how mutations disrupting these systems can influence energy balance
what do sensing organs in hypothalamus detect
circulating gut and appetite regulation hormones
how do sensing organs in hypothalamus detect concentration of circulating gut and appetite regulation hormones
many regions have incomplete blood brain barrier
how does the hypothalamus elicit a coordinate central response to oversee energy balance, and why have this many
combines peripheral signals (neural input, grehlin, peptide YY, leptin, other gut hormones); many signals as redundancy (make sure if one neuronal population or gene doesn’t work to allow compensation) and different causes (e.g. nausea vs full of food)
what 2 nuclei in hypothalamus are involved in fundamental central control of appetite regulation
acruate (bottom of brain) and paraventricular
where is the arcuate nucleus located
base of brain
what allows peripheral signals to directly activate the arcuate nuclei circuitry
peripheral signals such as nutrients, hormones, concentrations and temperature
what are the 2 separate neuronal populations within the arcuate nucleus
NPY/Agrp (neuropeptide Y/Agouti-related peptide) and POMC (proopiomelanocortin)
which neurone stimulates food intake, and which neurone inhibits it
NPY/Agrp stimulates, POMC inhibits
where are NPY/Agrp and POMC neurones located
NPY/Agrp located medially, POMC located laterally
where are the somas of these neurones
acruate nucleus
where do the axons from these neurones project for appetite
paraventricular nucleus and other regions of brain
how do POMC neurones reduce food intake
a-MSH (a melanocyte stimulating hormone) from POMC neurones binds to MC4R (melanocortin 4 receptor) receptor, agonising receptor
how to NPY/Agrp neurones maintain food intake behaviour
Agrp from NPY/Agrp neurones binds to MC4R receptor, antagonising it and blocking satietal signal
what are released to bind receptors in paraventricular nuclei
neuropeptides
what deficiency and mutation can cause morbid obesity (not usually responsible)
POMC deficiency and MC4R mutation
what do other brain input signals into paraventricular nuclei include
higher centres, amygdala (emotion, memory), other parts of hypothalamus (e.g. lateral), vagus to brain stem to hypothalamus
what does leptin provide
long term appetite regulation
what secretes leptin
cells in white adipose tissue
what happens when leptin binds to receptors in hypothalamic circuits
suppresses appetite (stimulates anorexigenic behaviours) and increases energy expenditure (thermogenesis)
evolutionary premise of leptin (adipostat mechanism)
well-nourished adult accumulates body fat, which increases leptin secretion and suppresses appetite
what is absent leptin, regulatory defect and leptin resistance in hypothalamus associated with
obesity; if high fat diet can cause leptin resistance (massive stimulation of appetite) which cannot be cured with leptin
what secretes ghrelin and when
cells in stomach in build up to meal
function of ghrelin
binds to hypothalamic receptors and increases short-term perception of hunger and urge to eat (stimulates NPY/Agrp neurones and inhibits POMC neurones)
what secretes peptide YY 3-36
cells in ileum and colon in response to meal
function of peptide YY 3-36
binds to hypothalamic receptors and reduces short-term perception of hunger and urge to eat (inhibits NPY release and stimulates POMC neurones)
what is cleaved off in peptide YY when full
first two amino acids
future of obesity treatment
gut hormones targeting only relevant circuits which are released daily without side-effects
comorbidities of obesity
depression, stroke, MI, sleep apnoea, hypertension, osteoarthritis, bowel cancer, peripheral vascular disease, gout
