Hunger and Satiety DSA

Question 1

Nutrient signals that indicate fullness, and therefore inhibit hunger, include:

Answer 1

• Rising blood glucose levels
• Elevated blood levels of amino acids
• Blood concentrations of fatty acids

Question 2

Hormones that supress feeling hunger

Answer 2

The hormones insulin and cholecystokinin (CCK) are released from the GI tract during food absorption and act to suppress feeling of hunger. CCK is key in suppressing hunger because of its role in inhibiting neuropeptide Y.

Question 3

Hormones that stimulate hunger

Answer 3

Glucagon and epinephrine levels rise during fasting and stimulate hunger. Ghrelin, a hormone produced by the stomach, is a hunger stimulant.

Question 4

Short-term appetite regulators (minutes to hours)

Answer 4

Ghrelin – produces hunger – from parietal cells of empty stomach – also stimulates hypothalamus release of human growth hormone releasing hormone
o Peptide YY – satiety – from enteroendocrine cells in ileum and colon – secreted in proportion to calories consumed – acts as ileal break – slows stomach emptying
o Cholecystokinin – satiety – from enteroendocrine cells of duodenum and jejunum – appetite-suppressing effect on brain

Question 5

Leptin

Answer 5

. Leptin serves as the brain’s indicator of the body’s total energy stores.
The functions of leptin are to:
Suppress the release of neuropeptide Y (NPY), which in turn prevents the release of appetite enhancing orexins from the lateral hypothalamus. This decreases appetite and food intake, promoting weight loss.

Question 6

Long term appetite regulators (weeks to years)

Answer 6

o Leptin – secreted by adipocytes in proportion to body fat stores
o Insulin – pancreatic beta cells, effect similar to leptin (but weaker)

Question 7

Neural control of appetite

Answer 7

 Emotions (stress), learned behavior provide signals to brain as well as nerves and hormones
 Stimuli such as gastric distention (fullness), secretory activity, and release of hormones from stomach, duodenum and adipose tissue regulate hunger and satiety

Question 8

Arcuate nucleus of the hypothalamus

Answer 8

 Hormones released from the GI tract and adipose tissue exert control here to regulate food intake and energy expenditure
Satiety center- VMN, PVN
Hunger center- lateral hypothalamus

Question 9

Two pathways of central nervous control of appetite

Answer 9

 Inhibition of food intake and increased metabolism [anorexigenic or POMC/CART (melanocortin) pathway]
 Stimulation of food intake and decreased metabolism [orexigenic or AGRP/neuropeptide Y (NPY) pathway]

Question 10

POMC/CART (Melanocortin pathway)

Answer 10

 Appetite-inhibiting neurons containing pro-opiomelanocortin (POMC)
 POMC cleaved to form α – MSH which binds to and stimulates MC4 receptors in the PVN and NTS to inhibit food intake and increase metabolism
 Insulin, leptin, and CCK stimulate this pathway- signal satiety
 Mutation of MC4 receptor linked to obesity (5% of acute childhood obesity)

Question 11

AGRP/NPY Pathway

Answer 11

 Hunger signals release of NPY to increase appetite
 Binds to Y1 receptors to initiate feeding behavior and store calories
 Agouti-related peptide (AgRP) also released- which is a MC4 receptor antagonist
 Ghrelin stimulates this pathway
 Stimulates desire for food and excites motor drives to search for food

Question 12

Vagal and Enteric Nervous Control

Answer 12

 In addition to regulation of GI motility and secretion, vagal nerve and enteric nerves regulate hunger and satiety
 Receptors sense:
 Chemicals present in food (glucose, aa, lipids)
 Changes in muscle tension (GI filling)
 Peptides released from endocrine cells after a meal, adipose tissue and nerves in gut (CCK, PYY, GLP, insulin, leptin, ghrelin)

Question 13

Vagal control

Answer 13

 Most vagal nerve fibers are afferent with information relayed to central vagal nuclei
 Pass through nodose ganglia to NTS and are coordinated with information received by hypothalamus
 Regulate food intake in response to peripheral signals
 Peptides which promote satiety and decrease feeding are present on vagal afferent fibers and activate receptors
 Signals initiated by stomach distention are also relayed via vagal afferents
 Some efferent signals are returned via vagal fibers as well (vagovagal reflex)
 Signals passing back to gut via these fibers change gut function based on afferent signals received by brain such as gastric filling, emptying, hormones, food content

Question 14

Endocrine Control

Answer 14

 Responsible for long-term regulation of food intake and body weight maintenance
 Includes hormones from pancreas, adipose tissue, and gut

Question 15

Hormones which decrease appetite

Answer 15

Insulin, leptin

Question 16

Insulin

Answer 16

 Released from pancreas, regulates glucose uptake and energy balance
 Can cross blood-brain barrier to bind to hypothalamic receptors which control food intake
 Clinical application: type 1 diabetic patients with inadequate insulin have increased food intake
 Additionally, presence of insulin antibodies increases food intake
 Potentiates satiety effect of gut hormones

Question 17

Leptin

Answer 17

 Released from adipose tissue, crosses BBB and tells brain how much fat is stored
 Receptors on neurons in arcuate nucleus
 Stimulates melanocortin pathway and inhibits neuropeptide Y/AgRP pathway
 As fat stores increase, leptin feeds back to inhibit feeding behavior and increase energy used
 Leptin resistance may be responsible for some obesity

Question 18

Gut hormones

Answer 18

 Some have effect on vagal afferents or cross blood-brain barrier and work directly on hypothalamus
 Include CCK, Peptide YY, Ghrelin, GLP-1

Question 19

CCK

Answer 19

 Released from duodenal mucosa in response to food higher in lipid content
 Inhibits feeding via effects on vagal afferent fibers (CCK1 receptors)
 Inhibits gastric emptying
 Potentiates effects of leptin

Question 20

Peptide YY

Answer 20

 Released from enteroendocrine (L) cells of ileum and colon by fat digestion products
 Inhibits gastric emptying and secretion
 Promotes short-term satiety
 Crosses blood-brain barrier and bind to Y2 receptors of hypothalamus
 Inhibits NPY neurons and stimulate POMC neurons

Question 21

Ghrelin

Answer 21

 Secreted by oxyntic gland cells of stomach in response to fasting
 Binds to GH receptor to stimulate release of GH
 Increases appetite
 Stimulates neurons of NPY pathway
 Acts directly on vagal afferents as well

Question 22

Other peptides

Answer 22

	Most have anorexic effect
	GLP-1
	Inhibits food intake, stimulates release of insulin, delays gastric emptying
	OXM
	Inhibits food intake
	PP
	Inhibits food intake

Question 23

Childhood obesity

Answer 23

 Mutation of MC4 receptor

Question 24

Obesity in general (three things are in red here)

Answer 24

 Long term regulation- endocrine system
 Leptin
 high level and resistance commonly associated with obesity
 PYY
 Low serum level associated with obesity
 Ghrelin
 Plasma level is low in obesity, therefore does not drive hunger in obese individuals
 Increases after weight loss due to dieting
 Decreases after gastric bypass surgery
 Also promotes GH release

Question 25

Treatment of Obesity- drugs

Answer 25

 Drugs with two MOA:
 Inhibition of pancreatic lipase with resulting malabsorption of fat leads to side effect of steatorrhea
 Central serotonin and NE reuptake inhibitors
-Increase feeling of fullness and satiety

Question 26

Treatment of obesity- surgery

Answer 26

 Jejunoileal bypass
 Gastric pouch
 Lap band procedure

Question 27

Summary of gastrointestinal peptides

Answer 27

7. Gastrointestinal peptides such as PYY, CCK and ghrelin are short-term regulators of food intake. PYY acts on the arcuate nucleus to suppress the appetite, whereas ghrelin acts on it to increase food intake. CCK and gastric distention activate vagal afferent fibers to the hindbrain to inhibit food intake and decrease the duration of a meal.