Lecture 11 Flashcards
(30 cards)
What is body mass homeostasis? What key factors are involved in this process?
Body mass homeostasis are essentially how your body maintains its current weight. The key factors that are involved in this process are appetite and the ability for your body to store energy as adipose tissue.
Explain the role of leptin (on fat synthesis and fat beta oxidation) in the set-point model for maintaining constant mass.
Some of the food that you eat is going to be stored as adipose tissue. That can be broken down for energy and heat. By breaking/building adipose tissue, the shrinkage/increase adipose tissue is going to cause the release of certain hormones.
Leptin is a hormone that is released in response to the increase of adipose tissue. It activates beta-oxidation and will inhibit fat synthesis and is usually going to be released after you have eaten to help you burn the fat that you have.
The reason leptin increases beta-oxidation and inhibits fat synthesis is so your body can maintain an energy balance and prevent excess fat accumulation.
What is the role of leptin? Where is this hormone released? Where does this hormone get sent, and under what conditions are levels of leptin high/low?
Leptin is a fuel-burning, appetite suppressing hormone which is released by your adipose tissue and sent to the brain.
It’s responsible for appetite suppression and is involved in heat regulation.
High levels of leptin are released after eating (body says you’re full already). When body fat decreases, leptin levels fall, and appetite increases.
As you start to burn through your fat, leptin will stop being released, signaling to your body that you are hungry.
When is insulin secreted? How and why does insulin suppress appetite?
Insulin is secreted in response to a rise in blood sugar levels after a meal. It also suppresses appetite by acting and binding to receptors in the brain. The reason that appetite is suppressed by insulin is because, through the act of eating and increasing blood sugar, this provides you with enough energy.
What does the hormone PYY do? When and where is this hormone released, and what tissue does this hormone target?
PYY is a hormone that is released by the small intestines and colon after you eat and is transported to the hypothalamus. It acts as an appetite suppressant by inhibiting the release of neuropeptide Y. As a result, hunger will be reduced.
Where is ghrelin secreted, and what are the effects of this hormone? What signaling pathway does ghrelin work by? Which individuals typically tend to have higher levels of ghrelin?
Ghrelin is a short-term orexigenic peptide which is secreted by the stomach. Ghrelin is one of the signals that tells you that you are hungry. It works through GPCRs. People who are trying to lose weight tend to have higher levels of ghrelin.
Where was leptin first identified, and what gene is leptin the product of? What occurs in animals/people which are homozygous recessive for the gene responsible for the production of leptin and why?
Leptin was first identified in obese mice. OB/OB = homozygous dominant means that the leptin gene is functioning and leptin can be produced.
Mice who were homozygous recessive (ob/ob) continually ate, had elevated cortisol levels, shivered, didn’t want to reproduce, had insulin resistance, and were super chunky.
The reason they kept eating is because they didn’t have the ability for their adipose tissue to release leptin, and for their brain to respond to the leptin to tell them they were full.
They shivered because leptin is also involved with heat regulation. Since they didn’t have leptin, they were also cold.
What happens to ob/ob mice when leptin injections were administered?
The mice were able to regulate their hunger, lose weight, and their body temperatures returned back to normal.
What occurs in individuals which are homozygous recessive (db/db) for the gene that encodes for leptin receptors in the brain?
They are not able to produce these brain leptin receptors, so they are not able to feel satisfied/full from their food. They are not able to regulate their heat/heat production, and they are also obese.
What happens to db/db mice when leptin injections are administered?
Nothing happens. db/db animals can still produce leptin, but they can’t respond to it because there’s no receptors.
The hypothalamic regulation of food intake and energy expenditure is going to be based upon what? Why?
It’s based on adipose tissue. There’s a signal that is sent to the adipose tissue that tells it that you need to mobilize/breakdown fat, fat needs to be stored, or that you have just ate. If there is an increase in adipose tissue, this will stimulate the secretion of leptin. The leptin will then signal the hypothalamus, and then the hypothalamus will decide if you’re full or not.
What does anorexigenic mean? What does orexigenic mean?
Anorexigenic: appetite suppressing
Orexigenic: appetite stimulating
What two appetite-related neurohormones does leptin affect in the brain? Are these hormones inhibited or stimulated by leptin? Are these hormones anorexigenic or orexigenic? What are the functions of these two hormones?
Neuropeptide Y (NPY): orexigenic (appetite-stimulating) hormone which sends signals to eat. Levels of this hormone increases during starvation. Leptin and insulin are responsible for inhibiting this hormone.
Alpha-melanocyte-stimulating hormone (alpha-MSH): anorexigenic (appetite-suppressing) hormone that signals you to stop eating. Leptin is responsible for activating this hormone. alpha-MSH will act on other receptors in the hypothalamus in order to decrease appetite and to stimulate processes that increase energy expenditure.
Explain how leptin, insulin, and PYY stimulate you to eat less and metabolize more.
In adipose tissue, the release of leptin is going to stimulate the secretion of alpha-MSH and leptin will inhibit secretion of neuropeptide Y (NPY) from arcuate neurons as well.
At the same time, insulin will inhibit the secretion of neuropeptide Y from arcuate neurons as well.
PYY is going to inhibit NPY secretion from arcuate neurons.
Since NPY secretion is inhibited, signals telling you to eat more will not be released. Since alpha-MSH is going to be released, signals that tell your body to eat less and metabolize more will be presents - meaning you will be less hungry and begin to metabolize more.
Explain how ghrelin stimulates you to eat more and metabolize less.
Ghrelin (hunger hormone) stimulates the secretion of neuropeptide Y from arcuate neurons. Secretion of NPY will inhibit some of the neurons which tell you to eat less and metabolize more. As a result of NPY secretion, this will tell you that you should eat more and store more energy, meaning that you are going to be hungrier and will metabolize less.
Through what signaling pathway does leptin increase transcription of the precursor for alpha-melanocyte-stimulating hormone? What is the precursor?
Leptin increases transcription of a gene for the precursor of alpha-MSH through the JAK-STAT pathway/receptor. Leptin receptors will dimerize when leptin bunds to the extracellular receptor domain, which causes JAK to phosphorylate 2 tyrosine residues in the receptor dimer. These phosphotyrosines become docking sites for signal transducers and activators of transcription through STATs SH2 domains.
When STATs bind to the phosphotyrosines with their SH2 domains, the STATs will become phosphorylated by the JAKs. The STATs will unbind from the phosphotyrosines after they have been phosphorylated by JAK and phosphorylated STATs will homodimerize, enter the nucleus, bind to DNA, and then activate genes.
What is thermogenesis? How does leptin play a role in increasing thermogenesis?
Thermogenesis is heat production.
The release of leptin leads to the release of norepinephrine. Using beta-adrenergic receptors, the binding of norepinephrine will lead to activation of PKA. As a result, an increase in the transcription of thermogenin occurs. Thermogenin will then be transported to the inner mitochondrial matrix to uncouple ATP synthase and the ETC to produce heat. More thermogenin means you will warm up more, and have more heat production.
Through which pathway does the increase in thermogenin occur? What other effects occur as a result of leptin-mediated secretion of norepinephrine?
Leptin-mediated secretion of norepinephrine from sympathetic neurons in the adipose tissue will allow for norepinephrine to stimulate beta-adrenergic receptors (responsible for activating adenylyl cyclase, followed by activation of PKA.) The activation of PKA will lead to the breakdown of fatty tissue.
The breakdown of fat will fuel the mitochondria in producing more heat since there will be more protons available, such that more heat can be released as a result of the thermogenin uncoupling the ETC from ATP synthase.
Why are leptin levels typically much higher in individuals than they are in non-obese individuals? What occurs as a result of this?
Leptin resistance occurs in obese individuals. Their bodies try to overcompensate for this and end up secreting a lot more leptin. This decrease in receptors for leptin occurs as a result of desensitization. Over time, as a result of higher-than-normal leptin secretion, their receptors become desensitized to the high levels of leptin secreted. Since there is less of a response, these individuals will continue to secrete leptin even more to compensate for the leptin resistance.
Why does insulin also inhibit appetite? Where and through what process does insulin inhibit appetite?
Insulin is released under conditions of high blood sugar, usually after a meal has been eaten. Insulin will interact with the hypothalamus such that it inhibits the release of orexigenic neuropeptide Y, and stimulates the secretion of anorexigenic alpha-melanocyte-stimulating hormone.
Why is there cross-talk between leptin and insulin pathways, and how does this cross-talk lead to the activation of genes responsible for inhibition of food intake?
Both contain a common secondary messenger which enables them to trigger the same downstream pathways/effects.
Activation of leptin receptors and insulin receptors leads to the phosphorylation of a common secondary messenger (IRS-2.) IRS-2 leads to the activation of PI3 kinase, which is responsible for activating genes responsible for the inhibition of food intake. Since both pathways activate IRS-2, it is more efficient to have this integration.
What is the role of adiponectin and where is it released from?
Adiponectin is important for appetite. This hormone is signaled when you are fasting and need energy and works through AMP-activated kinase. It’s made in the adipose tissue and circulates the blood and makes other organs sensitive to insulin. This hormone also prevents against atherosclerosis as well as inflammation.
Why does adiponectin make other organs more sensitive to insulin?
The reason that adiponectin makes other organs is because insulin will allow better glucose uptake in cells/organs, thus allowing cells to better utilize the energy that is available under times of starvation.
Through what pathway does adiponectin function? What is the result of activation of this pathway on fat breakdown/synthesis?
Adiponectin activates AMPK such that during times or fasting/exercise/starvation, it will aid in maintaining energy homeostasis by stimulating glucose uptake and increasing fatty acid oxidation in cells. Synthesis pathways will be shut off as a result of adiponectin activation of AMPK.
