Regulation of food intake Flashcards
What are the Neuronal centers that control feeding and satiety in the hypothalamus?
- Lateral nucleus (LH)
- Ventromedial nucleus (VM)
- Paraventricular nucleus (PV)
- Dorsomedial nucleus (DM)
- Arcuate nucleus (arc)
where does the hypothalamus receive signals to help with regulation of control?
- Neural signals from the GI tract
- Chemical signals from GI hormones
- Signals from adipose tissue
- Signals from cerebral cortex (sight, smell and taste)
Where does most of the integration signaling regulating food intake and energy expenditure happen?
Arcuate nucleus
what is the Anorexigenic pathway?
THe POMC/CART (pro-opiomelanocortin) in the arcuate nucleus will release a-melanocortin (a-MSH) on to the PVN
-these act on the MCR-4 receptor
this process will decrease food intake
this is activated by inulin, leptin and CCK
the POMC/CART also acts on the orexigenic pathway by inhibiting it via the release of a-MSH
what is the Orexigenic pathway
Hunger signals from Ghrelin will stimulate the AGRP/NPY of the arcuate nucleus
- release neuropeptide on to the PVN to stimulate food
- neuropeptide will bind to the Y1R receptor
- agouti-related peptide (AGRP) is also released to inhibit the MCR-4 (anorexigenic pathway)
how does the anorexigenic and orexigenic pathways influence each other?
Both pathways antagonize each other:
-peptides that stimulate the a-MSH pathway will inhibit the NPY system
-AGRP is an antagonist to MCR-4 and will inhibit the anorexigenic pathway
Clinical correlation of the POMC and MCR-4 genes
some cases of obesity have been related to mutations in the POMC and MCR-4 genes
genetic causes of obesity: Leptin
Leptin or leptin receptor gene deficiency
- Early onset server obesity
- infertility
- hypogonadotropic and hypogonadism
- hyperphagia
- infections
genetic causes of obesity: MC4R
Melanocortin 4 receptor gene mutation
- Early onset severe obesity,
- increased linear growth
- Hyperphagia
- hyperinsulinemia
- most common know genetic cause of obesity
- homozygous worse than heterozygous
genetic causes of obesity: Prader-Willi syndrome
Partial deletion of chromosome 15 or loss of paternally expressed genes
-Neonatal hypotonia
-slow infant growth
-small hands and feet
-mental retardation
-hypogonadism
-hyperphagia
elevated ghrelin
genetic causes of obesity: POMC gene
Loss of function of the Proopiomelanocortin (POMC)
- obesity
- red hair
- adrenal insufficiency due to ACTH deficiency
- hyperproinsulinemia
- hyperphagia
- pale skin
- cholestatic jaundice
by inhibiting the Vagal nerve how could it affect the feeding behavior and metabolism?
if the vagal activity is blocked, the amount of materia in the stomach no longer influences meal size
what is the Vagal, BTS, hypothaamus circuit?
Nucleus tractus solitarus is crucial in the interpretation and relaying of peripheral signals
Vagal signaling to the NTS is integrated with info recieved by the hypothalamus to produce the appropriate feeding behavior and metabolic responses
THe hindbrain is able to regulate food intale in response to peripheral signals even in the absence of higher centers
what is the function of the Lateral hypothalamic area?
Hunger center
-neurons project throughout the brain and release the oxigenic peptides melanin concentrating hormone (MHC) or orexins A and B
what is the function of the Ventromedial hypothalamic nucleus?
satiety center
what is the function of the Paraventricular nucleus:
THis nucleus contains neurons that in turn project to both the cerebral cortex and the areas of the brainstem
what is Ghrelin and what are its actions and what does it bind to?
Secreted in the stomach by endocrine cells
Binds to growth hormone secretagogue receptors (GHSR)
Stimulates neurons that release NPY
Actions:
- increase appetite
- increase gastric motility
- increase gastric acid secretion
- increase adipogenesis
- decrease insulin secretion (evidence for increase too)
Appears to initiate the feeding response
What does insulin do towards regulating feeding behavior and what are its actions?
BInds to receptors in POMC and NPY systems
- inhibits NPY pathway
- Stimulates POMC pathway
Actions:
- decrese appetite
- increase metabolism
in patients with type 1 DM there is an increase in food intake associated with a decrease in insulin
what does CCK do in the regulation of the feeding behavior
- Released by I cells in the duodenum
- Elicts satiety
acts on vagal, NTS, hypothalamus circuit
- decreases ghrelin
- increases gastric emptying when there is an increase in gastric distention
what does PYY do in regulation of feeding behavior?
Released by L cells of the ileum and colon following a meal
Binds to Y2R in the hypothalamus
- inhibits NPY neurons
- releases inhibition of POMC neurons
- promotes satiety
what does leptin do in the regulation of feeding behavior?
Secreted by cells in adipose tissue
Binds to receptors in POMC and NPY systems
- inhibits NPY pathway
- stimulates POMC pathway
Appetite supressing hormone
- decrease in appetite
- increase in metabolism
- decrease in ghrelin release
leptin in obese children
In obese children with congenital leptin deficiency, subcutaneous administration of recombinant leptin reduces fat mass, hyperinsulinaemia and hyperlipidaemia
However obesity in humans is often associated with high leptin levels and failure to respond to exogenous leptin ( leptin resistant)
Source, site of action, and effect: Insulin
source: pancreatic Beta cells
site of action: hypothalamus
effect: decrease in appetite
increase in metabolism
Source, site of action, and effect: Leptin
source: Fat cells and endocrine cells of the stomach
site of action:
-Hypothalamus, decrease in NPY, AgRP
increase in POMC
Vagal afferents
Effect:
- decrease appetite
- increase metabolism
- decrease ghrelin release
Source, site of action, and effect: CCK
source: I cells of the duodenum
Site of action: Vagal afferents
Effect:
- decrease appetite
- decrease gastric emptying
Source, site of action, and effect: PYY
Source: L cells of the ileum and colon
Site of action: hypothalamus
-decrease in NPY, and AgRP
-increase in POMC
stomach
Effect:
- decrease in appetite
- decrease in gastric emptying
- increase in metabolism
Source, site of action, and effect: Ghrelin
Source: Endocrine cells of the stomach
hypothalamus
large and small intestines
Site of action: Hypothalamus
-increase NPY and AgRP
vagal afferents
Effect:
- increase appetite
- decrease metabolism
- decrease leptin release
Summary integration of signals regulating food intake and energy expenditure
Adiposity signals are involved in the long term regulation of energy balance
while gut peptides modullate food intake on a meal by meal basis
How does Glucagon like peptide-1 affect the body
GLP-1
- Proglucagon derived peptide
- Co-secreted with PYY from L cells in the intestine
- Incretin
- levels rise after a meal and fall during fasting
- reduces food intake, suppresses glucagon secretion and delays gastric emptying
How does Oxyntomodulin affect the body
- Proglucagon derived peptide
- relleased from L cells of the intestine in response to ingested food and in proportion to caloric intake
- anorectic effect
how does Pancreatic Peptide affect the body?
- secreted from cells in the pancreatic islet of langerhans
- Putatively decreases food intake through Y4R in the brainstem and hypothalamus
How does Glucagon affect the body?
- secreted by a cells of the pancreatic islets
- increases blood glucose levels and insulin secretion
- reduces food intake
How does Amylin affect the body?
- Stored and relleased with insulin in response to food intake
- anorectic effects (inhibition of NPY release)
what is Anorexia nervosa? and what physiological changes are occuring?
Characterized by self starvation and excessive weight loss
Patients become severely manourished and significantly emaciated leading to endorinological and cardiological dysfunctions and abnormalities within the digestive, skeletal, and reproductive systems
Polymorphisms in genes in eating attitudes, the regulation of eating behavior, motivation and reward mechanism (AgRP)
Basal and pulsatile secretion of leptin is reduced in association with reductions in fat mass
Ghrelin resistance appears to be a conductive factor to a restrictive diet
Elevated levels of PYY
-might contribute to decreased nutrient intake and disordered eating psychopathology
