obesity and the endocrine control of food intake Flashcards
how body weight is controlled
by hypothalamus, which affects food intake and energy expenditure- input from leptin, gut hormones, and neural input (eg vagus nerve from brainstem)
DIAGRAM structure of hypothalamus+ most important part
most important part arcuate nucleus
arcuate nucleus
has incomplete brain barrier, so can access blood- has a STIMULATORY ie increase appetite(NPY/Agrp neuron) and INHIBITORY (POMC neuron) neuronal population (ie only CELL BODIES in arcuate nucleus)
CNS mutations affecting appetite
no NPY/Agrp mutations, but POMC deficiency can cause obesity, or MC4-R mutation (ie alpha MSH can’t bind)- thus no inhibition of appetite
how leptin works
when body fat high, leptin tells body that body fat is high enough, so it decreases food intake/increases expenditure by activating POMC/inhibiting NPY/AgRP neurones- thus affects arcuate nucleus
leptin resistance
even though leptin is high in fat ppl, they have resistance- thus INEFFECTIVE for weight loss
effect of lack of leptin and importance- include main OTHER effect
high appetite/low expenditure, immunosurpressed, stunted growth (ie body thinks its started to death)- thus these ppl can get leptin main other effect is INFERTILITY/irregular periods- LH/FSH low in both sexes, so giving leptin can help this- for women with general amennorhea, leptin often useful for skinny females
effect of insulin on appetite
basal insulin proportional to body fat, due to increased resistance as you weigh more- there are receptors in the - hypothalamus, which reduce appetite when stimulated- thus doesn’t ONLY affect glucose/a.a/lipid metabolism
largest endocrine organ
GI tract
DIAGRAM mechanism of gut hormone secretion
enteroendocrine cells have receptors on epithelium responding to lipids/carbs/proteins, which then release hormones into circulation, which affects enteric nervous system, has endocrine effects eg on pancreas or brain itself, and paracrine effects
structure of ghrelin
28 a.as’, with a fatty acid chain attached unlike other peptide hormones- enzyme called GOAT helps attach the fatty acid chain to it
mechanism of ghrelin
stimulates NPY/Agrp and inhibits POMC neurones in arcuate nucleus to increase appetite
what secretes PYY and GLP-1
L cells
structure of PYY
36 aas, which has proline and tyrosine chopped off once meal eaten
mechanism of PYY
inhibits ONLY NPY release, and stimulates POMC to decrease appetite
GLP-1 structure and precursor DIAGRAM
coded for preproglucagon gene which also codes for glucagon, thus a pro-glucagon molecule has GLP-1 and glucagon cleaved rapidly by DPP-4 enzyme to become INACTIVE, thus has SHORT half life
GLP1 and incretin effect
although pancreas releases insulin due to glucose, large amount of insulin release due to presence of glucose in GUT, as incretin produces hormones like GLP-1 which produces more insulin and reduces appetite
incretin based therapies
GLP-1 agonists and DPP-4 inhibitors, which have a longer half life- often used for diabetics, and even obese ppl (SAXENDA- high dose of GLP-1 agonist)
how gut hormones cause satiety
mainly post prandially (ie after meal), but also chronically, as in gut disease, hormones are high to allow gut to recover allow cause nausea when toxins are ingested, surpressing appetite
DIAGRAM how gut hormones can be used as drugs
problem with these hormones is short half life, thus conc. at which it’s useful not so long- thus hormones can be pharmacokinetically modified
comorbidities associated with obesity
stroke, diabetes, MI, depression, cancer, osteoarthritis
how genetics affect obesity
a lot, shown by twin studies, who are both fat
whats driving obesity epidemic DIAGRAM
we have toxic environment- thus those who are genetically prone get fat, those who are genetically resistant won’t be affected much
thrifty gene hypothesis
in olden days, genes that help with fat storage give u survival advantage- may explain partially why ppl fat today
