Regulation of Satiety Flashcards
Review the role of leptin in central regulation of feeding.
Leptin
- Released into blood by adipose tissue in response to feeding –> travels to brain –> binds to receptors on 1st order POMC/CART neurons in arcuate nucleus of hypothalamus –> stimulates POMC/CART neurons to release alpha MSH onto second order neurons in PVN of hypothalamus –> aMSH binds to MC4R receptors in PVN –> second order neurons communicate with vagus nerve via nucleus solitarius –> vagus carries out signals to GI tract that promote feeling of fullness so eating stops
- POMC/CART neurons can also release GABA onto NPY/AgRP neurons in arcuate nucleus and onto second order neurons in the lateral hypothalamus to inhibit them both and thus inhibit signals of hunger
Review the role of ghrelin in central regulation of feeding.
Ghrelin
Released into blood by stomach in response to hunger / sight/smell/thoughts of food –> travels to brain –> binds to receptors on 1st order NPY/AgRP neurons in arcuate nucleus of hypothalamus –> stimulates NPY/AgRP neurons to release NPY onto second order neurons in lateral hypothalamus –> second order neurons communicate with vagus nerve via nucleus solitarius –> vagus carries out signals to GI tract that promote feeling hunger and motivation for seeking food and also increases GH release from pituitary
NPY/AgRP neurons can also release GABA onto POMC/CART neurons in arcuate nucleus and onto second order neurons in the lateral hypothalamus to inhibit them both and thus inhibit signals of satiety
Peripheral control of food intake and energy balance involves short-term and long-term signals. What are examples of each of these types of signals?
Short term
- Ghrelin (+) hunger
- CCK, GLP-1, PYY (-) hunger
Long term
- Insulin and leptin (-) hunger
Describe the process of how short-term regulatory factors regulate feeding.
- When / where is ghrelin secreted?
- What are the functions of ghrelin?
What clinical conditions have lower levels of ghrelin associated with them?
What clinical conditions have higher levels of ghrelin associated with them?
What role does CCK play on the CNS with regards to hunger and satiety?
- What is peptide tyrosine tyrosine (PYY)?
- Where is it secreted from?
What is the role of PYY with regards to communication with the CNS related to hunger and satiety?
GLP-1 and GIP are released in response to […]
Food
- GIP (green) –> food in proximal small intestines
- GLP-1 (yellow) –> food in distal small intestines and early colon
Where / how is GLP-1 synthesized.
Where / how is GIP synthesized.
Synthesized by L-cells in the ileum from proglucagon.
Synthesized by K cells in the duodenum/jejunum from its own pro-hormone, pro-GIP.
What are the effects of GIP and GLP-1 on beta cells of the pancreas?
What are other locations where receptors for these hormones can be found?
GIP
- Bind to receptor on beta cell –> induce GPCR, Gas signaling –> insulin release
- Other receptors in adipocytes, brain, and GI tract
GLP-1
- Bind to receptor on beta cell –> induce GPCR, Gas signaling –> insulin release
- Other receptors in heart and vasculature, CNS/PNS, GI tract
What are incretins?
GLP-1 and GIP
What are the effects on the body of GIP?
Increase intestinal motility, increase insulin secretion, decrease gastric secretion and motility
GLP-1
- Where is this hormone produced/secreted?
- What is the stimulus to promote its production and secretion?
- What are its systemic effects?
- L-cells of ileum
- Carbohydrates, lipids, amino acids in ileum
- Release insulin, decrease gastric motility and secretion, increase CO, decrease appetite, decrease beta cell apoptosis and increase beta cell neogenesis, decrease glucagon secretion, increase glucose uptake in muscle and decrease glucose production in liver
How are GLP-1 and GIP levels impacted in type 2 diabetes?
How can GLP-1 analogues be used as therapy for type 2 diabetes?
Analogues have a longer half life in the blood b/c they are less susceptible to degradation by DPP-4, which inactivates GLP-1. Thus, they are able to increase beta cell responsiveness to glucose.
Can also give DPP-4 inhibitor to slow the inactivation of naturally produced GLP-1. Would depend on whether the person made normal amounts of GLP-1 still or if their levels had declined.
What could be the issue seen in this child?
Individual had mutation in leptin that made it less able to bind to receptor. Thus, levels of leptin are high in the blood but there is severely diminished leptin signaling, and functional leptin signaling is needed to regulate appetite and weight control.
What are the levels of leptin and ghrelin in obesity?
Leptin elevated
Ghrelin decreased
This is just demonstrating that the signals coming from the body are in the direction you’d expect for someone who is overfed. There are other behaviors or bodily pathways occurring that result in obesity, but the hormonal signals trend in the anticipated directions for one who needs to decrease intake of food.
What are the levels of leptin and ghrelin in anorexia nervosa (usually)?
Leptin low
Ghrelin high
This is just demonstrating that the signals coming from the body are in the direction you’d expect for someone who is starving. There is other CNS behavior happening that results in anorexia but the hormonal signals trend in the anticipated directions for one who need to take in food.
What are adipokines?
Adipokines are other hormones secreted by adipose tissue that are involved in long term regulation of energy balance. These include adiponectin and resistin.
Adiponectin
- Secretion is [….] proportional to body fat
- Protects from […]
- Has anti-[…] properties
- What is its role in feeding?
- inversely
- type 2 diabetes
- Increases insulin sensitivity
- Increases glucose uptake
- Increases energy expenditure
- atherogenic
- Works with leptin to activate POMC/CART neurons in arcuate nucleus
Resistin
- Secretion is […] proportional to body fat
- Increases risk of […]
- Relationship to obesity
- directly
- type 2 diabetes
- decreases insulin sensitivity
- decreases glucose uptake
- decreases energy expenditure
- link obesity with insulin resistance
