Regulation of Food Intake Flashcards
What is hunger?
internal state of an animal seeking food
What is satiety?
feeling of fulfillment or satisfaction
What brain region has complete control of appetite?
-No single brain region has complete control
What does the hypothalamus regulate?
- metabolic rate
- food intake
- body weight
What is the dual-center hypothesis?
- 2 appetite centers in hypothalamus (outdated due to oversimplification)
- one signals hunger (anorexic)
- one signals satiety (orexigenic)
What does the hypothalamus process?
-signals that modulate food intake and energy expenditure
What are the regions of the hypothalamus?
- arcuate nucleus (ARC)
- paraventricular nucleus (PVN)
- dorsomedial nucleus (DMN)
- ventromedial nucleus (VMN)
- lateral hypothalamic area (LHA)
What signals does the hypothalamus receive and from where?
- neural signals from GI tract (stomach filling/distention)
- chemical signals from nutrients in blood (glucose, amino acids, fats)
- signals from GI hormones (ghrelin, CCK, peptide YY)
- signals from adipose tissue itself (leptin)
- signals from cerebral cortex (sight, smell, taste)
____ is best-characterized region related to feeding behaviors
arcuate nucleus of hypothalamus
What are anorexic signals for the arcuate nucleus of hypothalamus?
-pro-opiomelanocortin (POMC) neurons
-cocaine and amphetamine related transcript (CART)
(+)
What are orexigenic signals for the arcuate nucleus of the hypothalamus?
-neuropeptide Y (NPY)
-agoutirelated peptide (AgRP) neurons
(-)
What do peripheral signals in the arcuate nucleus do?
cause release of specific neuropeptides from subpopulations of these neurons
What does the anorexigenic pathway do?
- reduces food intake and increases EE
- POMC/CART neurons release alpha-melanocyte stimulating hormone (alpha-MSH)
- alpha-MSH binds to MCR-3 on NPY/AgRP neurons to inhibit their activity
- Leptin is a well-characterized stimulator of POMC/CART anorexigenic pathways while inhibiting AgRP/NPY orexigenic pathways leading to reduced food intake
What does the orexigenic pathway do?
- increases food intake and decreases EE
- NPY/AgRP neurons release NPY
- NPY binds to Y1Rs on second order neurons to stimulate food intake
- AgRP is an MCR-4 antagonist, blocking the action of alpha-MSH
- Ghrelin is released from the stomach and activates NPY/AgRP neurons to stimulate food intake (stimulate weight gain)
Long-term metabolic regulation of energy balance or meal by meal basis: adiposity signals
long-term metabolic regulation of energy balance
Long-term metabolic regulation of energy balance or meal by meal basis: gut peptides
modulate food intake on meal by meal basis
What are the types of obesity genes?
- disruptions in leptin-melanocortin pathway
- SNPs in fat mass and obesity-associated gene
- developmental delay syndromes
- chromosomal rearrangements
What are examples of disruptions in leptin-melanocortin pathway?
- leptin- homozygous frameshift, nonsense, and missense mutations involving LEP and LEPR
- POMC deficiency
- MCR-4 - heterozygous mutations
- Prohormone convertase-1-deficiency, Albright’s Hereditary Osteodystrophy, SRC homology 2B (SH2B1) 1 deficiency
What is the SNPs in fat mass and obesity associated gene?
FTO
What is a developmental delay syndrome associated with obesity?
Prader-Willi
What is the vagal mediated reflex in satiety and feeding?
control energy homeostasis in short-term (homeostatic) and long-term (hedonic)
What is the NTS crucial for?
interpretation and relaying of peripheral signals
What is Ghrelin?
- secreted by
- binds to
- stimulates
- actions
- initiates
- peak
- secreted by oxyntic cells of stomach
- binds to growth hormone secretagogue receptors (GHSR)
- stimulates neurons that release NPY
- actions: increase appetite, gastric motility, gastric acid secretion, adipogenesis; decreases insulin secretion
- appears to initiate feeding response
- levels peak right before meals
What is insulin?
- binds
- actions
- disease
- binds to insulin receptors in NPY/AgRP (inhibitory) and POMC/CART (activates) systems
- actions: decreases appetite; increases metabolism
- influence of type 1 diabetes - increased appetite due to loss of insulin
What is peptide YY (PYY)?
- released by
- binds to
- releases
- released by L cells of the ileum and colon following a meal
- binds to Y2R on NPY/AgRP neurons to inhibit
- releases inhibition of POMC neurons
What is leptin?
- secreted by
- binds to
- actions
- secreted by adipocytes
- binds to POMC/CART (stimulates) and NPY/AgRP (inhibits) neurons
- actions: decreases appetite and ghrelin release; increases metabolism
What can congenital leptin deficiency cause?
obese children
-can by treated by sc administration of recombinant leptin
What is adult obesity often associated with?
elevated leptin and failure to respond to exogenous leptin (leptin resistance)
What is CCK?
- released by
- elicits
- acts via
- released by I cells in duodenum
- elicits satiety
- acts via vagal –> NTS –> hypothalamic circuit
What is glucagon-like peptide-1 (GLP-1)?
- derived from
- secretion
- when do levels change
- action
- proglucagon derived peptide
- co-secreted with PYY from L cells of intestine
- incretin molecule
- levels rise during meal and decrease during fasting
- action: reduces food intake, suppresses glucagon secretion, delays gastric emptying
What is oxyntomodulin (OXM)?
- derived from
- released
- action
- increase is proportional to
- proglucagon derived peptide
- released from L cells of intestine in response to ingested food
- action: decrease gastric motility and secretions
- increase is proportional to caloric intake
- anorexic effect
What is the anorexic effect?
-systemic administration of OXM can reduce food intake and body weight (maybe by suppressing ghrelin)
What is pancreatic peptide (PP)?
- secreted from
- decreases
- acts via
- secreted from cells in pancreatic islets of langerhans
- decreases food intake via Y4R in brainstem and hypothalamus
- may also act via vagus N
What is amylin?
- stored and released
- inhibits
- what effect?
- stored and released with insulin from pancreatic beta cells in response to food intake
- inhibits NPY release
- anorexic effect
What is glucagon?
- secreted by
- increases
- reduces
- secreted by pancreatic alpha cells
- increases blood glucose levels and insulin secretion
- reduces food intake
What hormones are released during feeding or just before?
CCK, amylin, insulin, glucagon
What hormones are released after feeding?
PYY, GLP-1, oxcyntomodulin
What hormone is released with hunger?
ghrelin
What hormones target vagal afferents?
CCK, amylin, insulin, glucagon
What hormones target brainstem?
PYY, GLP-1, OXM, leptin
What hormones target hypothalamus?
PYY, GLP-1, OXM, ghrelin
What hormone targets the arcuate nucleus?
leptin
What hormone targets the vagus N?
CCK, amylin, insulin, glucagon, ghrelin
What hormones limit size of meal?
CCK, amylin, insulin, glucagon
What hormones postpones need for next meal?
PYY, GLP-1, OXM
What hormone has a longer-term regulation of food intake?
leptin
What hormone increases food intake by increasing size and number of meals?
ghrelin
What hormones are from the pancreas?
amylin, insulin, glucagon
What hormones are from the ileum and colon?
PYY
What hormones are from the stomach?
ghrelin
What cells produce CCK?
I cells
What does obesity increase the risk for?
- cardiometabolic disease
- dementia/Alzheimer’s
- kidney disease
- certain cancers
- respiratory disease
- osteoarthritis
What are the treatments for obesity?
- lifestyle interventions
- bariatric surgery
- drug therapies
What are the 4 most common bariatric surgeries in the US?
- adjustable gastric band (“lap band”)
- Roux-en-Y gastric bypass
- duodenal switch (DS)
- vertical sleeve gastrectomy (“gastric sleeve”)
What is adjustable gastric band bariatric surgery?
“lap band”
- adjustable band around upper portion of stomach, restricts stomach’s capacity for filling
- can be adjusted upon weight loss/gain via small access port located just under skin
- patient’s lose 40-50% of excess weight
- diabetes resolves in 50-60% of patients
What is sleeve gastrectomy?
- left lateral portion of stomach is removed
- leaves banana shaped and sized stomach behind
- patients lose 50-75% of excess weight and diabetes resolves in 60% of patients
What is biliopancreatic division with duodenal switch (BPD-DS or DS)?
- sleeve gastrectomy is performed and large portion of small intestine bypassed
- decrease absorption of nutrients
- weight loss better than gastric bypass
- diabetes resolves in >90% of patients
What is Roux-en-Y gastric bypass?
- involves creating a small stomach pouch and bypassing 3-5 ft of small intestine
- used for >40 yrs
- stomach becomes size of egg
- restricts amount of food that can be consumed
- patients lose 50-75% of excess weight with good maintenance of weight loss
- diabetes resolves in 80% of patients
What are the effects of Roux-en-Y gastric bypass?
- reduced activity of mesolimbic reward pathway and other reward centers - especially when shown pictures of high caloric density food (decreased desire to eat)
- altered taste through changes in palatability and condition mechanisms
- increased gut hormones (GLP-1 and PYY increase as early as 2 d after RYGB surgery and remain elevated for 10 yrs)
- improved gut bacteria colony - related to improved inflammatory status
What is anorexia nervosa (AN)?
-characterized by self starvation and excessive weight loss
DSM-5 criteria
- persistent restriction of energy intake leading to significantly low body weight (in context of expected)
- either an intense fear of gaining weight or of becoming fat, or persistent behavior that interferes with weight gain
- disturbance in the way one’s body weight or shape is experienced, undue influence of body shape and weight on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight
Describe the gut-brain axis in anorexia nervosa
- polymorphisms of genes involved in eating attitudes, regulation of eating behavior, motivation, and reward mechanisms (AgRP)
- basal and pulsatile secretion of leptin reduced
- ghrelin resistance (fasting, so chronically elevated)
- elevated levels of PYY
What is bulimia nervosa?
characterized generally by binge-purging episodes (purging not necessarily self-induced vomiting)
- swollen parotid glands
- upper GI acid reflux, dysfunctional LES
- esophagitis and barrett’s esophagus (Barrett’s sign on hand)
- Mallory Weiss tear - life threatening
- heart and electrolyte disturbances
What hormones are released from the small intestine?
GLP-1
Oxcyntomodulin
