obesity and the endocrine control of food intake

Question 1

how body weight is controlled

Answer 1

by hypothalamus, which affects food intake and energy expenditure- input from leptin, gut hormones, and neural input (eg vagus nerve from brainstem)

Question 2

DIAGRAM structure of hypothalamus+ most important part

Answer 2

most important part arcuate nucleus

Question 3

arcuate nucleus

Answer 3

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)

Question 4

CNS mutations affecting appetite

Answer 4

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

Question 5

how leptin works

Answer 5

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

Question 6

leptin resistance

Answer 6

even though leptin is high in fat ppl, they have resistance- thus INEFFECTIVE for weight loss

Question 7

effect of lack of leptin and importance- include main OTHER effect

Answer 7

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

Question 8

effect of insulin on appetite

Answer 8

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

Question 9

largest endocrine organ

Answer 9

GI tract

Question 10

DIAGRAM mechanism of gut hormone secretion

Answer 10

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

Question 11

structure of ghrelin

Answer 11

28 a.as’, with a fatty acid chain attached unlike other peptide hormones- enzyme called GOAT helps attach the fatty acid chain to it

Question 12

mechanism of ghrelin

Answer 12

stimulates NPY/Agrp and inhibits POMC neurones in arcuate nucleus to increase appetite

Question 13

what secretes PYY and GLP-1

Answer 13

L cells

Question 14

structure of PYY

Answer 14

36 aas, which has proline and tyrosine chopped off once meal eaten

Question 15

mechanism of PYY

Answer 15

inhibits ONLY NPY release, and stimulates POMC to decrease appetite

Question 16

GLP-1 structure and precursor DIAGRAM

Answer 16

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

Question 17

GLP1 and incretin effect

Answer 17

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

Question 18

incretin based therapies

Answer 18

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)

Question 19

how gut hormones cause satiety

Answer 19

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

Question 20

DIAGRAM how gut hormones can be used as drugs

Answer 20

problem with these hormones is short half life, thus conc. at which it’s useful not so long- thus hormones can be pharmacokinetically modified

Question 21

comorbidities associated with obesity

Answer 21

stroke, diabetes, MI, depression, cancer, osteoarthritis

Question 22

how genetics affect obesity

Answer 22

a lot, shown by twin studies, who are both fat

Question 23

whats driving obesity epidemic DIAGRAM

Answer 23

we have toxic environment- thus those who are genetically prone get fat, those who are genetically resistant won’t be affected much

Question 24

thrifty gene hypothesis

Answer 24

in olden days, genes that help with fat storage give u survival advantage- may explain partially why ppl fat today