Hunger and Satiety DSA Flashcards
Nutrient signals that indicate fullness, and therefore inhibit hunger, include:
- Rising blood glucose levels
- Elevated blood levels of amino acids
- Blood concentrations of fatty acids
Hormones that supress feeling hunger
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.
Hormones that stimulate hunger
Glucagon and epinephrine levels rise during fasting and stimulate hunger. Ghrelin, a hormone produced by the stomach, is a hunger stimulant.
Short-term appetite regulators (minutes to hours)
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
Leptin
. 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.
Long term appetite regulators (weeks to years)
o Leptin – secreted by adipocytes in proportion to body fat stores
o Insulin – pancreatic beta cells, effect similar to leptin (but weaker)
Neural control of appetite
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
Arcuate nucleus of the hypothalamus
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
Two pathways of central nervous control of appetite
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]
POMC/CART (Melanocortin pathway)
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)
AGRP/NPY Pathway
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
Vagal and Enteric Nervous Control
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)
Vagal control
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
Endocrine Control
Responsible for long-term regulation of food intake and body weight maintenance
Includes hormones from pancreas, adipose tissue, and gut
Hormones which decrease appetite
Insulin, leptin
Insulin
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
Leptin
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
Gut hormones
Some have effect on vagal afferents or cross blood-brain barrier and work directly on hypothalamus
Include CCK, Peptide YY, Ghrelin, GLP-1
CCK
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
Peptide YY
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
Ghrelin
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
Other peptides
Most have anorexic effect GLP-1 Inhibits food intake, stimulates release of insulin, delays gastric emptying OXM Inhibits food intake PP Inhibits food intake
Childhood obesity
Mutation of MC4 receptor
Obesity in general (three things are in red here)
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
Treatment of Obesity- drugs
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
Treatment of obesity- surgery
Jejunoileal bypass
Gastric pouch
Lap band procedure
Summary of gastrointestinal peptides
- 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.
