Role of the GIT in Obesity Flashcards
Weight is regulated in the
Hypothalamus
Which nucleus in the hypothalamus regulates body weight?
Arcuate nucleus
What are the two classes of nerves in the arcuate nucleus?
NPY (NPY and AgRP)
POMC (CART and aMSH)
NPY nerves release _______ when they fire which ________ appetite
NPY and agouti-related protein (AgRP); increase appetite
POMC nerves release ________ when they fire which _________ appetite
CART (cocaine and amphetamine related transcript) and aMSH; decrease appetite
Which hormones from the stomach regulate food intake at the arcuate nucleus?
Ghrelin
Which hormones from the small bowel regulate food intake at the arcuate nucleus?
CCK, PYY, GLP-1, Oxyntomodulin, Uroguanilin
Which hormones from the pancreas regulate food intake at the arcuate nucleus?
insulin, amylin, PP
Ghrelin ________ appetite by activating _______
increases; NPY and its mRNA
Leptin ________ appetite
decreases;
Ghrelin and leptin work
antagonistically
Ghrelin rises _________ and drops __________
before a meal; after a meal - diurnal variation
ILP-5 ________ appetite via ________
increases; relaxin5 receptor (GPCR)
ILP-5 is expressed
colon; less so in ileum, none in jejunum
Which hormone is the most powerful driver of hunger?
NPY > Ghrelin > ILP-5
CCK is made in the
upper bowel/I cells of small intestine
CCK is made as a
preprohormone
Which CCK peptide has the highest potency?
CCK8
CCK is secreted from
I cells in small intestine
The half-life of CCK is
short (~mins)
CCK stimulates
emptying of the gallbladder and release of digestive enzymes
CCK acts through which receptors?
CCK1 and CCK2
CCK _________ food intake and is involved in _________
inhibits; digestion
CCK mediates its effects mainly via
CCK1R on the vagus nerve
Why doesn’t CCK work as a tx in obesity?
Reduces food intake but increases number of meals
PYY is made in the
L cells of the GIT (ileum)
PYY ________ food intake and _______ body weight
reduces; decreases (chronic)
PYY is cleaved by
DPP4; the enzyme that degrades GLP-1, oxyntomodulin
What is the action of PYY?
reduces food intake (and body weight if used chronically); increases feelings of satiety (but also nausea)
Oxyntomodulin is a product of which gene?
Glucagon
Oxyntomodulin is released from
L cells of the lower small intestine in response to food
Oxyntomodulin ________ food intake and _________ energy expenditure
reduces; increases
Oxyntomodulin may mediate its effects via which receptor?
GLP-1 R
Oxyntomodulin is inactivated by
DPP4
T/F Oxyntomodulin is more potent than GLP-1
True
What is the benefit of combining PYY and oxyntomodulin?
they work synergistically to further reduce food intake
GIP
gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide
What are the incretin hormones that stimulate insulin secretion?
GIP and GLP-1
GIP is released from
duodenal and jejunal K cells after ingestion of nutrients
What is the action of GIP?
stimulates insulin release, activates lipoprotein lipase (clears fat from plasma for storage)
What are the actions of GLP-1?
increases period of postprandial satiety, slows gastric emptying
GLP-1 decreases intake of
food quantity, calories, and fluid
Liraglutide
human GLP-1 w/attached FA molecule (enters brain more readily)
What is the concern with using liraglutide?
it increases HR; BP drops with weight loss but the HR does not change
Uroguanylin is produced in
the distal gut
What are the actions of uroguanylin?
decreases food intake via the brain; decreases intestinal fluid absorption via the gut
What happens to leptin following weight loss?
leptin decreases dramatically with weight loss (70% below fasting) and starts to rise only in proportion to weight gain
What happens to ghrelin following weight loss?
ghrelin increases (it still follows diurnal variation with meals) tf more hungry
What happens to PYY following weight loss?
PYY decreases; making you more hungry
What happens to CCK following weight loss?
CCK decreases; making you more hungry
Why do hunger hormones increase and satiety hormones decrease following weight loss?
Defensive mechanism to maintain body weight
T/F Hunger hormones and satiety hormones go back to baseline 1yr after weight loss
False; Ghrelin is still increased, PYY and CCK are still decreased - this is why it is so hard to maintain weight loss
T/F Gut hormones play an important role in the defense of body weight
True; levels of hunger hormones (ghrelin) are increased and satiety hormones (CCK, PYY) are decreased even 1yr post weight loss
How do gut bacteria influence body weight?
processing of dietary indegestable polysaccharides to short-chain fatty acids (butyrate, acetoacetate) which protect against bowel cancer - this increases calories and fat absorption in the liver; increased activity of LPL and tf fat storage
