Lecture 22: Regulation of Food Intake Flashcards
Where are the neuronal centers that control feeding and satiety located and what are they?
- Hypothalamus
- Lateral nucleus (LH)
- Ventromedial nucleus (VM)
- Paraventricular nucleus (PV)
- Dorsomedial nucleus (DM)
- Arcuate nucleus (Arc)
What type of signals does the hypothalamus receive?
- Neural signals from GI tract
- Chemical signals from nutrients in blood
- Signals from GI hormones
- Signals from adipose tissue
- Signals from cerebral cortex (sight, smell and taste)
Where does most of the signaling regulating food intake and energy expenditure occur?
Arcuate nucleus via 2 pathways: anorexigenic and orexigenic
What is the anorexigenic pathway?
- α-melanocortin (α-MSH) released by pro-opiomelanocortin (POMC) neurons of arcuate nucleus
- α-MSH binds to MCR-4 present in second-order neurons of paraventricular nuclei
What is the orexigenic pathway?
- Hunger signals stimulate release of Neuropeptide Y from arcuate nucleus
- NPY binds to Y1R of paraventricular nuclei
- Agouti-related peptide (AGRP) is also released; antagonist of MCR-4
How do the arcuate nucleus pathways antagonize eachother?
- Peptides that stimulate the α-MSH pathway inhbit the NPY system
- AGRP is an antagonist of MCR-4
What hormones activate the POMC and what do they do to the AGRP/NPY?
- Insulin, leptin, and CCK all activate the POMC neurons (anorexigenix path)
- They inhibit the AGRP/NPY (orexigenic path)
What hormone activates the AGRP/NPY neurons?
Ghrelin
Mutations in the POMC and MCR-4 genes have been related to what pathology in some cases?
Obesity
What is the vagal –> NTS –> hypothalamus circuit?
- Vagal afferents relay info from stomach to NTS via the sensory ganglian of the vagal nerve (Nodose ganglion)
- Hypothalamus will then use info to produce the appropriate feeding behavior and metabolic responses using vagal efferents
Even in the absence of higher centers’ input what is able to regulate food intake in response to periphera signals?
The hindbrain
Where does Ghrelin come from and what does it do?
- Secreted in the stomach by endocrine cells
- Binds to growth hormone secretagogue receptors (GHSR)
- Stimulates neurons that release NPY
- Increases appetite, gastric motility, gastric acid secretion, and adipogenesis
- Decreases insulin secretion
Where is insulin released from and what does it do?
- Binds to receptors in POMC and NPY systems
- Inhibits NPY pathway and stimulated POMC pathway
- Decreases appetite
- Increases metabolism
In patients w/ DM type I there is an increase in food intake associated w/ a _______ insulin
Decreased insulin
Where is CCK released from and what does it do?
- Released by I cells in the duodenum
- Elicits satiety
- Acts on vagal –> NTS -> hypothalamus circuit to decrease ghrelin
- Decreases gastric emptying, which increases gastric distention
Where is PYY released from and what does it do?
- Released by L cell of the ileum and colon following a meal
- Binds to Y2R in the hypothalamus
- Inhibits NPY neurons
- Releases inhibition of POMC neurons
Where is Leptin secreted from and what does it do?
- Cells in adipose tissue
- Inhibits NPY pathway
- Stimulates POMC pathway
- Appetite-suppressing hormone: decreases appetite and ghrelin release and increases metabolism
Obese children w/ a congenital leptin deficiency can be treated how; what is the outcome?
- Subcutaneous administration of recombinant leptin
- Reduces fat mass, hyperinsulinaemia, and hyperlipidaemia
Obesity in humans is often associated w/ what leptin issue?
High levels of leptin and failure to respond to exogenous leptin (leptin resistance)
What does Glucagon-like peptide-1 (GLP-1) do, where is it secreted from and when is it secreted?
- Proglucagon derived peptide
- Co-secreted w/ PYY from L clls in the intestine
- Incretin (decrases blood glucose levels)
- Levels rise after a meal and full during fast
- Reduces food intake, suppresses glucagon secretion, and delays gastric emptying
What is Oxyntomoduin, where is it secreted from, and what is its effect?
- Pro-glucagon derived peptide
- Released from L cells of the intestine in response to ingested food and in proportion to caloric intake
- Anorectic effect
What does Pancreatic peptide (PP) do, where is it secreted from?
- Secreted from cells in the pancreatic islets of Langerhans
- Decreases food intake directly through Y4R in the brainstem and hypothalamus
- May also act via the vagus nerve to produce anorectic effects
Where is glucagon secreted from and what does it do?
- Secreted by α cells of the pancreatic islets
- Increases blood glucose levels and insulin secretion
- Reduces food intake
Where is Amylin released from and what are its effects?
- Stored and released with insulin in response to food intake
- Anorectic effects (inhibition of NPY release)
What are the particularly promising gut hormone targets that are candidates for successful obesity therapies?
GLP-1, oxyntomodulin, leptin, and peptide YY
What are the 3 most commonly performed procedures for bariatric surgery?
1) Roux-en-Y gastric bypass (RYGB)
2) Adjustable gastric banding (AGB)
3) Biliopancreatic diversion (with or w/o duodenal switch)
How does RYGB alter endogenous gut hormones responses to a meal; which patients had the most weight loss?
- Elevated responses are seen in GLP-1 and PYY as early as 2 days after RYGB and may remain elevated for >10 years after RYGB
- Patients w/ the most weight loss after RYGB also had the highest levels of these gut hormones
Which bacteria has been shown to be increased following RYGB; and what are the effects?
- Proteobacteria
- Improvement of weight, inflammation and metabolic status after surgery was associated w/ increased bacterial variety
How does RYGB affect taste?
- Appears to alter taste through unconditional and conditional mechanisms
- May be exerting its effects on food selection and preference through any one of the taste function domains such as: sensory discriminative (stimulus identification), hedonic (ingestive motivation), and physiological (digestive preparation)
What are the effects of RYGB on the liver, gastric pouch, portal vein, and pancreas?
Liver: decreased glucose output
Gastric pouch: increased gastric emptying
Portal vein: altered nutrient and hormonal sensing
Pancreas: increased insulin release
What is the effet of RYGB on the Ileum?
- Increased GLP-1
- Increased PYY
- Increased OXY
- Increased Bile acids
In anorexia nervosa what are the levels of leptin and adiponectin like?
Both are decreased, likely in association with reductions in fat mass!
In anorexia nervosa what are the levels of ghrenlin and peptide YY like; why are each of these hormones significant in this disease?
Both are increased
- Ghrelin (orexigenic) resistance appears to be conductive factor to a restrictive diet
- Elevated PYY (anorexigenic) might contribute to decreased nutrient intake and disordered eating psychopathology
Why is elevated CRH in the hypothalamus significant in anorexia nervosa?
- Leads to increased cortisol (stress hormone)
- Decreased TSH, which leads to decreased T3 (thyroid hormone)
- Decreases FSH and LH, which decreases testosterone (males/females) and decreased estradiol (females)
