Role of the GIT in Obesity

Question 1

Weight is regulated in the

Answer 1

Hypothalamus

Question 2

Which nucleus in the hypothalamus regulates body weight?

Answer 2

Arcuate nucleus

Question 3

What are the two classes of nerves in the arcuate nucleus?

Answer 3

NPY (NPY and AgRP)

POMC (CART and aMSH)

Question 4

NPY nerves release _______ when they fire which ________ appetite

Answer 4

NPY and agouti-related protein (AgRP); increase appetite

Question 5

POMC nerves release ________ when they fire which _________ appetite

Answer 5

CART (cocaine and amphetamine related transcript) and aMSH; decrease appetite

Question 6

Which hormones from the stomach regulate food intake at the arcuate nucleus?

Answer 6

Ghrelin

Question 7

Which hormones from the small bowel regulate food intake at the arcuate nucleus?

Answer 7

CCK, PYY, GLP-1, Oxyntomodulin, Uroguanilin

Question 8

Which hormones from the pancreas regulate food intake at the arcuate nucleus?

Answer 8

insulin, amylin, PP

Question 9

Ghrelin ________ appetite by activating _______

Answer 9

increases; NPY and its mRNA

Question 10

Leptin ________ appetite

Answer 10

decreases;

Question 11

Ghrelin and leptin work

Answer 11

antagonistically

Question 12

Ghrelin rises _________ and drops __________

Answer 12

before a meal; after a meal - diurnal variation

Question 13

ILP-5 ________ appetite via ________

Answer 13

increases; relaxin5 receptor (GPCR)

Question 14

ILP-5 is expressed

Answer 14

colon; less so in ileum, none in jejunum

Question 15

Which hormone is the most powerful driver of hunger?

Answer 15

NPY > Ghrelin > ILP-5

Question 16

CCK is made in the

Answer 16

upper bowel/I cells of small intestine

Question 17

CCK is made as a

Answer 17

preprohormone

Question 18

Which CCK peptide has the highest potency?

Answer 18

CCK8

Question 19

CCK is secreted from

Answer 19

I cells in small intestine

Question 20

The half-life of CCK is

Answer 20

short (~mins)

Question 21

CCK stimulates

Answer 21

emptying of the gallbladder and release of digestive enzymes

Question 22

CCK acts through which receptors?

Answer 22

CCK1 and CCK2

Question 23

CCK _________ food intake and is involved in _________

Answer 23

inhibits; digestion

Question 24

CCK mediates its effects mainly via

Answer 24

CCK1R on the vagus nerve

Question 25

Why doesn't CCK work as a tx in obesity?

Answer 25

Reduces food intake but increases number of meals

Question 26

PYY is made in the

Answer 26

L cells of the GIT (ileum)

Question 27

PYY ________ food intake and _______ body weight

Answer 27

reduces; decreases (chronic)

Question 28

PYY is cleaved by

Answer 28

DPP4; the enzyme that degrades GLP-1, oxyntomodulin

Question 29

What is the action of PYY?

Answer 29

reduces food intake (and body weight if used chronically); increases feelings of satiety (but also nausea)

Question 30

Oxyntomodulin is a product of which gene?

Answer 30

Glucagon

Question 31

Oxyntomodulin is released from

Answer 31

L cells of the lower small intestine in response to food

Question 32

Oxyntomodulin ________ food intake and _________ energy expenditure

Answer 32

reduces; increases

Question 33

Oxyntomodulin may mediate its effects via which receptor?

Answer 33

GLP-1 R

Question 34

Oxyntomodulin is inactivated by

Answer 34

DPP4

Question 35

T/F Oxyntomodulin is more potent than GLP-1

Answer 35

True

Question 36

What is the benefit of combining PYY and oxyntomodulin?

Answer 36

they work synergistically to further reduce food intake

Question 37

GIP

Answer 37

gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide

Question 38

What are the incretin hormones that stimulate insulin secretion?

Answer 38

GIP and GLP-1

Question 39

GIP is released from

Answer 39

duodenal and jejunal K cells after ingestion of nutrients

Question 40

What is the action of GIP?

Answer 40

stimulates insulin release, activates lipoprotein lipase (clears fat from plasma for storage)

Question 41

What are the actions of GLP-1?

Answer 41

increases period of postprandial satiety, slows gastric emptying

Question 42

GLP-1 decreases intake of

Answer 42

food quantity, calories, and fluid

Question 43

Liraglutide

Answer 43

human GLP-1 w/attached FA molecule (enters brain more readily)

Question 44

What is the concern with using liraglutide?

Answer 44

it increases HR; BP drops with weight loss but the HR does not change

Question 45

Uroguanylin is produced in

Answer 45

the distal gut

Question 46

What are the actions of uroguanylin?

Answer 46

decreases food intake via the brain; decreases intestinal fluid absorption via the gut

Question 47

What happens to leptin following weight loss?

Answer 47

leptin decreases dramatically with weight loss (70% below fasting) and starts to rise only in proportion to weight gain

Question 48

What happens to ghrelin following weight loss?

Answer 48

ghrelin increases (it still follows diurnal variation with meals) tf more hungry

Question 49

What happens to PYY following weight loss?

Answer 49

PYY decreases; making you more hungry

Question 50

What happens to CCK following weight loss?

Answer 50

CCK decreases; making you more hungry

Question 51

Why do hunger hormones increase and satiety hormones decrease following weight loss?

Answer 51

Defensive mechanism to maintain body weight

Question 52

T/F Hunger hormones and satiety hormones go back to baseline 1yr after weight loss

Answer 52

False; Ghrelin is still increased, PYY and CCK are still decreased - this is why it is so hard to maintain weight loss

Question 53

T/F Gut hormones play an important role in the defense of body weight

Answer 53

True; levels of hunger hormones (ghrelin) are increased and satiety hormones (CCK, PYY) are decreased even 1yr post weight loss

Question 54

How do gut bacteria influence body weight?

Answer 54

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