Description: The passage is intended to concentrate on ampk activator. The author is going to talk about a protein NPK which has become one of the most suitable protein as the target against obesity for treatment during the last thirty years. It is related to AMPK in the hypothalamic control of energy metabolism in a more molecular level.
I’m going to talking in a more molecular level, not my previous speakers and I want to talk about a protein NPK, during the last thirty years, it has become as one of the most suitable protein as target against obesity for treatment.
When we will try to look for anything to try to versity, you can see in this pitch of the world that instead of a West East Asia or Africa in the rest of the world, it’s about twenty percent of population.
These are high prevalence of obesity and how it is possible well to do an eeveelution human being has acquired new skills to survive in the environment, however, disappearing a new human amo basis maybe it’s due to the easy access to the food, maybe to the less physical activity we make and also the quality of food we take.
So to understand the molecular level, how bully weight, it’s regulating, we have to understand a term, that is the energy balance, this term is to understand easily an equation between energy intake, so Flynn we take every day and energy spend it to is the energy we use to survive to maintain our temperature or to doing activities, physically active activities.
So in normal conditions, it leads an optimal metabolic status with a normal body weight and optimum metabolic studies in peripheral thisis, however, when these are with disruption in this energy balance.
For example, with an increase in energy expenditure, a decrease in energy Spenser and increase in energy intake, it leads to an increase in body weights of appearing obesity and overweight an accumulation of lipid droplets in peripheral dishes leading to an obesity and metabolic disorders.
So who is the room console that lists the relation of this energy balance? This room control is there both elements that is placed on the basis of their brain and its importance, its ability to sense every nutrients and hormones that are informing about our energy status and produce a response to maintain these energy balance.
So in this, ayat Allah knows we have different neuronal populations that are able to sense this peripheral or minuto or mono and nutrition signals and produce a response to modulate glucose and lipid metabolism in peripheral tissues and importantly to middle aid neuropeptides involved in feeling behavior like origin averted eyes that induce feelings or unreasonable diets that reduce blood appetite to modulate food intake and moreover, this nucleus populations in the hypothalamus are able to move late energy spent by modulating the thermogenic program in the brown adipose tissue.
So which is the role that plays mpk in this energy balance regulation? While the importance of MBK is that, its role in regulation switching on and switching off the pathway of the fatty acids metabones information the production of the athlete fatty acid metal this battery, the relation of this pathway leads to the production of fatty acids.
So in Britain, apathy is right, so switching on, switching out this production, the fatty acids could lead to store fatty acids in peripheral tissues as fat or in other cases in turn, the fatty acids in the mitochondria to produce energy, so to understand how this part of the pathway rose, these are seminal papers.
If we block the fidelity synthase, we can see how individuals stop to eat and how individuals became leaner, because they are with the NPK with the Italians blockage in our experiment in a seminal paper, we found that in knockout mice male and female.
When we look out fast enzyme, there’s a reduction in body weight onto in gender with a reduction due to a reduction in fat instead of lean mass and accompany a complainer, but a reduction in the feeding pattern, so with the role of NPK in this important metabolic pathway regulating energy balance.
Mpk is approaching, it’s important is do it with sensitivity to the energy levels by the ambach aim be ATP ratio and it’s able to activate it by phosphorylation by different upstream kindnesses or inactivation by the first relation by several phosphatases, so this protein is inactivated, it leads to an increase of energy spend, so become linear individuals.
In contrast, when mpk is activated, induce reduction in an expenditure and induction of flinte becoming obese individuals to understand how rows mpk in the neurons that regulate food intake disturbance in the arcade nucleus the tartarean lgp neurons that induce feeling or pmc neurons that block fill.
If we block with an account without mpk in this neurons that induce feeling, we say how this individuals became leaner, so they’re blocking the actions of the inducer recipe, however, when we block NPK, this protein in the meeting the neurons that are lead to innovate feeling, we saw the opposite effect that is sorry to understand another peripheral signal well known as this railing that has a known effect over food intake.
Because one of the subtlety signals from body and increase adiposity in the last years has said that NPK is the best the unique mediator of the effect of over food intake of the almond or peptide real realm, so in this picture, there are a lot of peripheral signals peripheral signals that are already clinic that induce for you to take an energetic signals that reduce food intake.
We can see that all studies have determined that when FinTech is increased, it is mediated by an increase in NPK, so implicit iteration and when food intake is decreased, it is an activation of the NPK, so we have seen how is the role of MBK in the full Intel regulation.
So now we’re going to see what is the Routan, what is the role of NPK in the other equation in the other term of the equation of the energy balance the energy expenditure, so the energy expenditure in human is mainly to do smell carrion or in the brown adipose tissue the brown adipose tissue is different from the white latest issue, because half instead of having one big lipid droplet of berry, it’s full literally with doubles, full of mitochondria that are going to carry on the thermogenesis.
So thermogenesis or in order to maintain the temperature in, when looking further for the room controller the room, controller nucleus in the brain for this energy spend, we saw that the epithalamus with their several nucleus are able to sense these peripheral hormones and peptides and throw the sympathetic nerve and the Rafah pallidum and inferior oliver are going to modulate the thermogenic problem in the brown adipose tissue by activating uncoupling protein 1 and producing heat and thus reducing a body weight well to see how mpk is regulating.
This energy spent its energy balance, I’m going to show you some studies we have done in the last years in laboratory of carlos de gusano, one of the most important is the regulation of the thyroid hormones and thermogenesis in brown adipose tissue and how is mpk mediating these effects.
When we train, when we trade rats with d3, so with the lab and portray Liam’s individual, we show that we see that these animals, I portrayed animals, don’t eat as much as normal rats, however, they become leaner.
When we analyze what happens with NPK the activation of the fattest metabolic pathway in the hypothalamus, we saw that rated T 3 theta drats has had less levels of activations of MV k1 and when we see what happened in the brown adipose tissue in the thermogenic program that carried the innate expenditure, we say that when we trade with t3 hyper thirteen rats have more CP 1 and markers of thermogenesis and thus increasing energy Spencer and get leading to a leaner furniture moreover these analysis about the sympathetic nervous activity.
When we inject in the ventral medial nucleus of the hypothalamus t3 the activation of the thermogenic in brown adipose tissue is doable activation of the sympathetic nervous system, so in order to block this effects of t3 our mpk, we decided to inject to activate, this implicated was innovated by this way in the different nucleus of the hypothalamus the ventromedial that leads the regulation of energy expenditure and the earthquake that leads the revelation of the behavior.
So we decided to inject viruses encoding a specific form of mpk that was a type active and we found that when we traded, I peripheral rats with NPK instead of being leaner, they become to gain weight, so they would reverse this planet type.
However, they weren’t different in for intake and this markers of thermogenic that were upregulated during in t3 animals when we traded with NPK various both absolutely reverse, so animals start to gain weight by decreasing their energy expenditure to see simply how this hormone titled hormones regulate energy balance or phenotype.
We can see this picture how 2 3 modulates NPK in the ventromedial simulate the energy spending creasing thermogenic problem in brown adipose tissue and can regulate a quick nucleus in a GP and BMC neurons to modulate fully take the other work.
What I want you to say to the show is about nicotine and energy balance, I’m sure that more of you have here that you have a friend or when stop smoking has gained weight, I’m sure about that, so in this case, we decided to inject to trade rats with nicotine and we show this normal rats.
When we traded with nicotine, we saw that Lee kichan decrease body weight gain, so rats became leaner and they tended to have a very lower feeding pattern, but importantly, when we stopped to trade with nicotine these rats, we showed that he wanted to gain a lot of weight that in compression are more than known to the rats.
So they become a not obese, but they gain a lot of weight and they normalize the feeding pattern, so what happened with this energy expenditure in rats, because nicotine have changing in some way this energy balance, so we found that nicotine increase temperature of rats.
So it can explain how Raja were leaner and moreover, we analyzed what happened with the pro, a thermogenic brown adipose tissue and we found that thickening induced this thermogenic Brown and thus inducing a reduction in body mass.
Moreover, we found that after treatment with nicotine, this is the the area where is the brown adipose tissue located in and in rodents and after 48 hours of treatment, we saw how new kitchen could increase temperature to increase thermogenic program in the brown adipose tissue.
So then we decided to assess whether MBK was involved in the regulation and when we chatted with nicotine, we saw it was an innovation of the activation of MBK, so we say that we decided to try to trade these rats with the same viruses will try to the hyper threaded rods and we found that when we tried rats with this viruses activating this protein that with nicotine was inactivated, we could reverse the body weight gain.
We can also reverse this thermogenic program that was activated during nicotine, so MBK was mediating the effects over energy spanning two by negative, so it’s same picture, then it should be fall with, I prefer rats or I prefer dames and I wanted to show in this picture how mpk could be important to modulate, these peripheral signals to integrate this peripheral signals and modulate the body weight by modulating energy Spencer increasing or decreasing thermogenic problem in brown manifestation and also feeding behavior by modulating neuropeptides in the crate nucleus.
So the message I want you to say is this protein, it’s very important to be one of them, the target for treating obesity, because implied involved in the regulation of energy balance mobility also food intake and the thermogenic prong in the most important tissue that is involved in energy Spencer does a brown alga station, I want to design my mentor Simon my supervisors Carlos Dagestan and Miguel Lopez, so I forget to put here and these are all the collaborators we are working with, so thank you very much.