Members Webinar

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Speaker 1 • 03:13
Welcome, everybody. We are pleased to welcome you to our second webinar of the ECN. Me and my colleague, Niels Sienackers are very delighted that a lot of people are already waiting to starting at our webinar and are present here today. As part of the Early Career Network, we are also of course part of the Basel, which is also part of the European Association for the Study of Obesity. We try to connect young researchers together across the country to bring not only basic clinical research, but also clinical practice. With this webinars, we also try to find where are the interests of everyone in our Early Career Network to try to get more members, and also to perhaps in the future see if we can have other educational opportunities for young researchers. And I also now want to give the word to my colleague Nele Senackers to introduce our

Speaker 2 • 04:14
speaker of today. Good evening everyone. I’m very delighted on behalf of the Belgian Association to introduce associate professor Dr. Tanya Adam from Maastricht University. And as a colleague, it’s especially nice to introduce her. And Dr. Adam, she’s a biopsychologist with a PhD in nutrition physiology and a postdoctoral training at the University of California. Her research focuses on the gut-brain axis and the interaction with metabolic signals, the brain reward system, and eating behavior, and especially in the context of obesity, weight loss and weight maintenance. And she combines lifestyle intervention trials with some mechanistic studies using non-invasive imaging to better understand weight regulation. And we are very pleased to have her with us tonight. So Tania, the floor is yours.

Speaker 3 • 05:08
– Thank you very much, Nile. And welcome everyone at the webinar. And thank you all for inviting me to this webinar. webinar. So you introduced my title already. And in preparation of this webinar, I also wanted to familiarize myself a little bit with obesity numbers, overweight numbers in Belgium. And for that, I looked at the latest OECD reports, and then I found out it’s actually not the latest that I depicted here. So there’s a 2025 one out now, but the numbers haven’t very much and as you can see, Belgium is here within the OECD countries pretty much in the middle with about 50% of overweight and this is self-reported data and 16% of obesity. So given the knowledge, hold on my clicker, yeah, my clicker is working. Given the knowledge about the diverse causes of obesity, the lifestyle interventions, which include both nutrition and exercise components are still very popular as a potential strategy for preventing and treating obesity. And both components are behavioral with physiological determinants, but also physiological consequences. However, it also appears that these lifestyle interventions are not always equally successful. Over the past two decades, there have been many groups of great scientists that have significantly improved our understanding of the physiological and behavioral mechanisms involved in weight loss and weight maintenance. But weight regain after weight loss still remains one of the most crucial problems in obesity therapy. And this is a meta-analysis, for example, this is from 2001, but this is still relevant and this is still pretty much the same as it looks now, independent or not regarding the pharmacological treatment options that we have these days. So this is a meta-analysis of 29 long-term weight loss studies, and it shows that more than half of the weight lost was about regained within the two years following and that over 80% of the original weight lost was regained within five years. And therefore the question still remains, how long-term weight loss can be successfully achieved to improve quality of life, but also of course, to prevent the chronic comorbidities associated with obesity such as type 2 diabetes and cardiovascular disease. Obesity is linked to numerous brain-related conditions and problems, including decreased cognitive function, reduced cerebral blood flow, for example, also increased inflammation, and these relationships can be direct or indirect. And identifying those relationships provides important information about the targets for prevention and treatment of obesity. In general, for the setup of this presentation, I wanna give you first an overall, an overview insight in general mechanisms to bring everybody onto the same page. And then I wanna come to some studies that we are doing and that our collaborative people that we collaborate with are doing and the latest results of those studies. So one of our main interests here is what role does the brain as the master coordinator of balance basically, especially the hypothalamus that are associated with physiology and behavior play and finding preventive and treatment strategies for obesity. It’s not only balanced in terms of eating behavior, also balanced in terms of temperature regulation, thirst regulation, sleep, and so forth. And as you will see later in the presentation, I have it where a nutrition department where Nele and I work now. So nutrition is placed very prominently in the middle, but you will find out later in the presentation that especially for my and my group’s interest, insulin plays a very important role within that inner action. But a guiding question for us is anyways, why doesn’t the eat less exercise more paradigm? Not, why does that not work? And just want to start at the beginning for everyone, the regulation of food intake under normal, healthy, and perhaps even ideal circumstances, which we also consider the homeostatic regulation of food intake. And so hunger and satiety generally as two components of the energy intake balance of the overall energy balance are regulated with different systems. So we have the nervous system and you see the nervous system relationship or interaction depicted here with the gray lines. The nervous system connects the stomach for example, certain stomach receptors play an important role here. So the more your stomach is distended under ideal circumstances, the faster you feel full. These receptors signal your brain that you have eaten enough. And this happens with the help of the autonomic nervous system. And within this nervous system, the parasympatheticus, the rest and digest system, and the vagus nerve, which composes the biggest part of the parasympathetic nervous system, plays a crucial role. But then we also have the orange arrows here and that depicts the endocrine system. So both your brain and your body do produce hormones and your body produces so-called hunger hormones such as krelin and satiety hormones, for example, PYY, CCK, but also GLP-1, but also insulin. These signals are long or short-term signals and they reach the brain via the bloodstream. So this figure is explaining homoesthetic food intake regulation. So when this system is functioning, we neither gain nor lose weight. So if everything is so well regulated, then why do we have an obesity issue? And that brings us to a question, takes one step back, and that is the question, why do we eat at all? And I put out some quotes here for you. Those are just a few quotes that show that we eat for all kinds of reasons. So for example, one quote is I use food for the same reasons an addict uses trucks to comfort, to soothe or to ease stress. So we eat for all kinds of various reasons that have very little to do with hunger in the physiological sense. And that brings us to the second system in the brain that plays an important role here. This is the hedonic system or the brain reward system. So the brain reward system originated as an ancient evolutionary adaptation and is designed to promote survival by reinforcing behaviors crucial for life such as eating and mating. So whenever you engage in those behaviors, your brain reward system is active and that signals you that you should repeat that behavior in the near future. So we eat, for example, because it tastes good or because you’re in good company and that gives you pleasure and that creates a sense of reward. And that can also occur even when your body isn’t experiencing any form of energy, physiological energy deficit. So previously I explained those two systems now. Previously it was thought that the homeostatic and the reward system were separate entities. But in recent years, there’s been increasing support for the simultaneous activity during eating. For example, it appears that the production of leptin, one of the satiety hormones can inhibit the hedonic value of food. Besides leptin, other homeostatic signals such as ghrelin and insulin also have receptors in the brain reward system. Well, if we have two systems and everything is regulated, why are there people who can’t stop eating? And this is an important question for me because I have quite some clinical background in a psychosomatic clinic dealing with the treatment of obesity. And that was a crucial question of those patients. Why can I just not stop eating? And I’ve been experienced that firsthand and watched those and gave company to those patients. And it was really evident that they just could not stop eating. So what we have to pay close attention to is another critical area. And that is the blood brain barrier right here. So the blood brain barrier protects the brain by forming a tight and very selective boundary between the brain and the periphery. And the purpose is to keep out harmful substances, bacteria, pathogens, and so forth. So the blood brain barrier that you see in the red circle here, which is at the arcuate nucleus located in the hypothalamus is very unique because it’s much more permeable than in most other parts of the brain. And information about which hormones can actually cross that blood brain barrier can provide important information about the therapeutic application of that particular hormone. For example, for decades, and I include myself I did my PhD thesis all on GLP-1 for four years. So for decades, we tried to stimulate GLP-1 in the periphery to promote satiety through the known of what we thought was the known pathway. So now we actually do know more. And that is the original theory that we had, which was very simple. food enters the gut, the gut releases GLP-1, GLP-1 travels through the bloodstream into the brain, GLP-1 induces more GLP-1 release within the brain and appetite is suppressed. But we do realize now that there’s a critical flaw in that previous assumption that we had because we know now that pre-probe glucagon neurons which do produce GLP-1 in the brainstem, they lack receptors for circulating GLP-1. and the gut derived GLP-1 cannot directly stimulate those brain cells. So central GLP systems operate independently. This is what our conclusion now is, driven by physiological signals such as gastric distention and neural inputs. So this is basically what we know now. Fairly recently that GLP-1 is one molecule with two modes of action. So the peripheral GLP-1 that we have been kept ourselves busy with for a long time does actually act as a hormone and circulates via the bloodstream, but it mostly regulates blood sugar. Whereas the central GLP-1 acts more as a neurotransmitter. And that is actually the GLP-1 we associate with the regulation of appetite now. There’s one hormone, however, that is different and that is insulin. So, insulin has receptors in both the homeostatic and the reward system. And so since the early 1990s, we’ve known that virtually almost all the insulin present in the brain originates from the periphery, and that insulin can cross the blood-brain barrier through a saturable mechanism. And this is very important to keep in mind, insulin also has a clearly different role in the brain compared to the periphery. In the periphery, we know insulin as an anabolic hormone that is important for glucose uptake in muscle, but in the brain, where glucose uptake is insulin independent, it acts as a catabolic signal, acting as a satiety and a reward signal, in the sense that the more insulin that goes to the brain, the more we, the more satiated we feel, but also not just the homeostatic satiated part, but also the reward aspect of the whole aspect is that we feel more satisfied. So insulin is very important for us in order, or insulin reception is extremely important for us to stop eating, to feel full, to feel like we have enough, and yeah, generally to stop eating. So that is like just a small introduction, And I just want to quickly summarize that for you. Hold on, I click up. No, I’m going way too far now. Yeah, okay, so here’s the summary. Before we move on, here’s the summary to like wrap up this part. So insulin receptors are widespread throughout the brain, especially in areas relevant to cognition and feeding. It’s an important satiety signal for homeostatic food intake regulation, but also for the reward perception that we get from food. It passes the blood-brain barrier through a saturable receptor mechanism. So this is very different from, for example, the GLP-1 hormone. And then I want to come back to my figure from the beginning and after the background story, I would like now go to the disruption of brain reward and how it plays a role for the maintenance or yeah, the continued existence of obesity and why it makes it so hard to actually lose weight. So early studies, when this whole research or like when brain imaging got introduced in the whole satiety research, the early studies often compared obese individuals with lean individuals. And they found that BMI dependent activation in areas of taste, motivation, but also emotion in response to high calorie visual stimuli were depending on the level of obesity that the participant presented with. And so they suggested it as a gateway to overeating and the development of obesity, that activity in the brain reward system. Subsequently though, and with the knowledge of the importance of peripheral signals for the brain, further questions have been raised here. Namely, is it actually the obesity that is responsible for changes in brain responses for example, visual food stimuli, other researchers use oral stimuli such as milkshakes or other rewarding aspects of food. Is that associated with obesity or is it associated with the metabolic changes that are the driver in that brain response here? So we do know the well-known people consequences of obesity are the development of insulin resistance, the insensitivity of the receptor to insulin and other issues here. So initially those studies that wanted to find out what the role of insulin resistance actually plays in brain reward activation was executed in animals. And so there’s one hallmark, I would call it like one of the hallmark experiments that paved the way to understand brain insulin resistance. And that is a study from Diane Fieklewicz. And so they gave a sucrose solution to rats and the rats perceived that as very pleasurable and very rewarding. And so they were willing to work for this. And so the number of active lever presses that you see on the Y-axis here, basically is an indication of how rewarding that fluid was for the rat. So then they found out when they give insulin and leptin into the ventricle, that the reward those animals perceived from the super solution was significantly decreased. The following experiment was that they put the animals on a six week cafeteria diet, just like what our students eat a lot on a daily basis, pizza, spaghetti, a lot of sweet foods, and they repeated the experiment. And so what they found, I’m gonna go too fast again, sorry. What they found is that insulin and leptin actually, after that six week high calorie diet, we’re not able anymore to inhibit the reward that those animals perceived from the sucrose solution. And those were the first indicators where scientists thought like, hey, there is most likely and probably insulin resistance in the brain. So we tried to translate those experiment into the human field. And so we conducted a large multi-center study with like 2,400 participants. This is the person you see here, that is Matthias Drummen. That was the PhD student who was on the study. And the study was called the PREVIEW study. It was like a EU sponsored study. And the aim of the study was to determine if a high protein diet in combination with high or medium exercise was superior to conventional moderate protein diet in combination with the same types of exercise for weight loss maintenance after weight loss and the prevention of type 2 diabetes in adults with pre-diabetes. So basically the incidence of type 2 diabetes was the primary outcome measure. So the main hypothesis of the study was that high protein diet would be superior to the recommended diet for weight maintenance after weight loss and for the prevention of type two diabetes. And this is how the study basically was set up. So participants had an initial weight loss period on a very low calorie diet that was a Cambridge weight plan. It’s like, you know, a fluid weight loss diet. They had that for eight weeks and the goal or the prereq for being included in the intervention was that they had to lose at least 8% of their initial body weight. And then they were randomized into the high and medium protein condition in combination with either high or medium intensity physical exercise. And then you see that the whole intervention lasted for three years. And 203 participants from that whole study came or were contributed from Maastricht. And so measurements were like in oral glucose tolerance tests, other blood parameters, such as inflammatory markers. We looked at food diaries, accelerometry, body composition, urinary nitrogen to check for the protein intake and so forth. So there were a total of several clinical intervention days with measurements, but for us, predominantly interesting, were those two that are circled in red because those two were the MRI sessions. So 39 participants from the Maastricht University agreed to participate in the brain imaging part of the study and they had a brain scan at baseline and they had a brain scan one year into the intervention. So what did we do here? In the scanner participants watched blocks of either high calorie foods, low calorie foods or neutral foods and they were randomized. And we looked at the brain activation in response to those food cues. Always with in the back of our minds, like, you know, is it now the insulin sensitivity that is responsible for what we see and the activity or is it the body mass, body mass index that is the most relevant component here? So what we found is that insulin resistance was actually associated positively with the brain reward activation in insulin singular gyrus, which are like, you know, well-known brain reward areas. And we didn’t find any relationship between BMI or body fat with brain reward activation. So in translation, that means the more insulin resistant the participant was, the stronger the brain reward system was activated. And like what I said in the beginning, if you remember an active brain reward system signals you that you want more of this, what you’re just doing. So we also found in that same previous study that protein intake, So the higher the protein intake, the lower the brain reward activation. So the protein intake seemed to be somewhat protective for that brain reward activation. So this could play an important role in long-term effects within a weight loss intervention and a weight loss paradigm and the prediction of the success of those interventions. So in summary, just to wrap this part up, the brain reward response to food stimuli was associated with insulin resistance and was independent of PMI or body mass. And protein intake during the weight maintenance period was inversely associated with changes in brain reward activity. protein intake therefore may support weight loss maintenance through beneficial changes in brain reward responses to food cues. We know that protein is always mentioned in the literature as being very satiating, but so here we also have an example that this might also mechanistically be transferred through activity in the brain reward areas. So that led us to the assumption that insulin resistance may be an important target for successful weight loss. and for successful weight loss maintenance. So, yeah, if insulin resistance in the brain prevents a proper satiety perception, actually, then weight loss is becoming very hard for people. If you’re not able to perceive the satiety signals that you’re getting anymore, then there is no physiological reason for you to stop eating. So the next question is, how can we improve brain insulin sensitivity? And first I want to explain the technique or like show you the technique that we’re using here in Maastricht quite a bit. And that is the nasal, intranasal insulin supplementation. And so a lot of that work has been done by people in our group, Peter Joris and Kevin Nyssen. and that’s why I put their pictures up here too. So this is basically the technique. So nasal insulin reaches the brain by bypassing the blood brain barrier. And instead of traveling through the bloodstream, it uses the direct highways basically from the nasal cavity to the central nervous system. And by performing tasks with an insulin spray compared to a placebo before and after intervention, we can see whether insulin sensitivity has changed. And so the participants receive the insulin spray while they’re in the scanner or the placebo spray. So I want to show you one of the examples from our collaborators, from Steffi Kuhlmann’s lab that we’re working with quite a bit from Tübingen in Germany. So they looked at the changes of brain reward activation after insulin spray compared to placebo. And the outcome measure basically here was the wanting for high calorie sweet foods in lean and in obesity or in lean participants and obese participants. So the yellow bars that you see are the women, the black bars that you see are the men. And the bars actually indicate the difference between placebo and insulin spray. So this is what you see. And then you see that after insulin compared to placebo in the lean group, the wanting for high calorie sweet food significantly decreased while in obese, especially in obese men, the wanting for that high calorie sweet food increased despite the nasal insulin spray. So what else can we use to improve central insulin sensitivity? So this is another study showing that exercise also improves central insulin sensitivity. So on the B part, you see the pre and post eight week exercise brain reaction towards the insulin spray. Here they measured that as the cerebral blood flow change, which also is related to brain insulin sensitivity. And on the C bar, you see the comparison group that had no exercise. And you can see that exercise significantly increased brain insulin sensitivity in that group. So we have basically the protein intake, we have exercise, and then we’re not a nutrition department if we’re not looking at nutrition. So how can nutrition possibly help with increasing central insulin sensitivity? And this is a fairly recent study that was led by our postdoc Kevin Nisen. You saw the picture before. And he looked at the effects of mixed nuts for 16 weeks every day versus no nuts for 16 weeks as the control period. and that was separated by an eight week washout period. So those nuts, that was 60 grams, 395 kilocalories that the participants consumed every day. They did not gain weight throughout that period. I think this is an important side note. And they basically replaced their food instead of like, you know, ate it on top. And so they could, with the help of nasal insulin application, see that there were six clusters that showed increased insulin sensitivity after the intervention, namely in the occipital lobe, in the frontal lobe, and in the middle frontal gyrus. So other aspects of improving brain insulin sensitivity are, for example, behavioral factors that can restore insulin sensitivity. And then peripheral insulin sensitivity and basically manipulating the central insulin sensitivity through the periphery. So conditions that are known to be associated with peripheral insulin resistance are for example, stress, cortisol actively inhibits insulin release and supports beta cell apoptosis, but also a lack of sleep, we should mention here. So one mechanism that could be relevant here is the increased inflammation that goes along with stress and sleep. So interventions that do improve those type conditions also would be possibility to improve central insulin. sensitivity. So in summary, I want to wrap this up and hope you found throughout the presentation and that I could convince you that insulin is an important satiety signal in the brain, that insulin resistance in the periphery does go along with insulin resistance in the brain, that an interrupted satiety perception due to insulin resistance in the brain may pave the road for overeating and the development, but also the maintenance of obesity. We’ve seen that exercise does help restoring insulin sensitivity in periphery, but also in the brain. We’ve seen that nutrition does improve insulin sensitivity in both periphery and the brain, that stress reduction might help restoring this. And I hope I could make the case here that insulin sensitivity should be an important target for brain health and as a prerequisite for weight loss and weight loss maintenance, as well as for brain health in an aging population. And with that, I’m gonna close with a fun group and we need a new picture because on this picture, Nele is not yet, but in the next one, she will be. So yeah, thank you all. I’m looking forward to your questions.

Speaker 1 • 37:13
– Thank you, Tanja, for the nice presentation. I already have a question. I was wondering if, as you told in the beginning of your presentation that GLP-1 can’t cross the blood-brain barrier, then I was thinking, okay, So then now we treat people with GLP-1 analogs or GLP-1 and GIP analogs and they do lose weight or would it then be your hypothesis that it is because they also reduce insulin resistance and it’s not because we give supra-physiological doses of GLP-1 or?

Speaker 3 • 37:56
Well, I think, you know, what makes those pharmacological treatments outstanding is is that they do cross the blood-brain barrier. And so our peripheral GLP-1 does not, but the medication is engineered in a way that it can cross the blood-brain barrier. And I think that is why it works basically. So they’re called dual agonists because of the composition of the medication, but they’re also a dual or triple agonist in the sense that they directly reach the brain. So they work as a neurotransmitter. They work in the periphery as a hormone and thereby also as an incretin lead to increased insulin sensitivity in the periphery. So it’s a benefit on several different levels basically.

Speaker 2 • 38:57
– Thank you, a very nice presentation. And I also invite everybody that’s listening to your presentation to ask questions in the chat. Obviously, nutrition related question. Can we already say how much of the protein, is it more that it affects by affecting the satiety signals or is the main effect through the rewards valuation of those foods? Can we already substantiate, is it one or the other more?

Speaker 3 • 39:28
– We can substantiate that, but my guess, since the proteins would not reach the brain directly, my guess would be in the periphery. So yeah, but I mean, we don’t have, so there is no direct link that I would connect to the brain here. So it should like go through the peripheral route.

Speaker 2 • 39:54
– Yeah, and based on the previous study, because it was quite a big study. Can we also translate it into practice because we have the whole protein hype at the moment. And I think you mentioned that the protein that there were protein percentage cutoffs used but can you based on the previous studies say like, okay we should go for the 1.2 grams that we know or the 0.8 or should we eat more protein in the morning? Is that something that was investigated?

Speaker 3 • 40:23
So the time of day was definitely not investigated. And I know that, you know, we just had like, you know a recent presentation here that was very interesting on protein. So the protein intake or the protein need also depends on your situation. So if you are a top sporter, you obviously need more protein because you have more muscle damage and you need more replacement than the average person. I know that the previous study as the medium protein value that was based on the 0.8 grams per kilogram body weight and the high protein was the 1.2 grams. I think for the average person, where I would consider myself an average person, I would think that that is plenty. But yeah, depending on your situation, you would need more, obviously.

Speaker 1 • 41:29
Then we also have some questions from the chat, and there is a question about ethnicity consideration and insulin sensitivity and brain response. Do you see differences?

Speaker 3 • 41:42
Yeah, that is very interesting because like, you know, when I did my postdoc in San Francisco, after that I moved to LA and worked at USC for a few years. And Los Angeles, everybody knows that there is a really rather big Hispanic population. And so my pilot study, because I wanted to start using MRI in satiety research. And my pilot study was in Latino kids. And so because they’re prone to develop even more insulin resistance than other ethnicities. And so there, that link clearly, we could lay that link exactly like this list. So I think there is a clear ethnic component in that, in the sense that you’re more or less prone to develop insulin resistance. And I think certain ethnicities are more at risk than others.

Speaker 2 • 42:53
– And then we have a very practical question because now the nuts are everywhere in the nutrition guidelines and we should eat them, but can we even recommend them or should we be combining them with nasal insulin?

Speaker 3 • 43:07
– So the interesting question is like, you know, like what I would also expect from the audience is like, you know, well, if nasal insulin works so good, why don’t we use nasal insulin as a medication? And that hasn’t, we don’t obviously. So the nuts are generally, I think a good way to, that helps, but the problem with the nasal insulin supplementation is that it’s more of a mechanistic approach in order to really try and isolate the reaction of the brain. Because there is several studies that show that what we do with the nasal insulin really predominantly stays in the brain. So we hardly have any effect from that on the peripheral insulin sensitivity. And I think the goal or the approach should always be a holistic one. So improve the brain insulin sensitivity and improve the peripheral insulin sensitivity at the same time. And since I don’t see any, any medical prescription of nasal insulin so far. I think the nuts are a safe way.

Speaker 1 • 44:35
– And a question perhaps, which is a bit leading on the past question, and can brain insulin sensitivity also be recovered in patients with type two diabetes, or could it be an explanation why people with type two diabetes, or it’s more difficult for them to lose the same amount of weight with, for example, the GG-LP1 analogs?

Speaker 3 • 44:59
Yeah. That would be based on the science that is out there at this point. That would be my theory. So that was also the point that I was trying to make, that if we re-establish sensitivity to our signals, that this is a gateway to weight loss because all of a sudden people are enabled again to perceive satiety actually and that makes weight loss possible. So say the question again.

Speaker 1 • 45:38
– That if it’s possible in people with type two diabetes to restore the brain insulin sensitivity or perhaps you’re not able and that’s perhaps why you tend to lose less weight than the same person with the same BMI, for example, with that type 2 diabetes? Yeah, so the second part I think I

Speaker 3 • 46:03
answered, you know, I would like say yes to that second part and there is quite a bit of data in type 2 diabetes that shows that insulin sensitivity, that patients can regain insulin sensitivity in the brain. So this is a flexible system. So this makes us very hopeful actually.

Speaker 1 • 46:24
And the science that is already out there, then is it by exercise or is it more than the proteins or how did they restore it then in people with Maltodevitz?

Speaker 3 • 46:36
– It’s not related to nutrition so much other than weight loss per se, but there’s definitely exercise studies that show those results.

Speaker 1 • 46:49
– Okay.

Speaker 2 • 46:52
– Then going back a bit more to the mechanistic part, what kind of gut brain axis related metabolites are involved in people living with obesity?

Speaker 3 • 47:05
Well, like, you know, right now we’re looking at the fatty acids, for example, because the assumption would be that they would be able to cross the blood brain barrier and they are associated with brain or with insulin in the brain. So they’re kind of like, you know, a gateway keeper a little bit for this. So that would be something interesting to look at. So we’re like in the process right now working with a cohort in Switzerland that can provide syrup or spinal fluid where we try to figure out how do the fatty acids, for example, move from the periphery to the brain. Another aspect would be the inflammatory markers. But I got to say, in terms of like what crosses the blood brain barrier, I feel like there is still a lot of work that needs to be done. Like what we know is really a lot of that is coming from animal research and yeah so that’s still a field where a lot of work can be done or has to be done.

Speaker 2 • 48:18
Do you believe that this is a field that will contribute to the personalized nutrition, personalized medicine, should we be phenotyping or do you see us phenotyping patients based on brain insulin sensitivity in the future?

Speaker 3 • 48:33
Possibly, yeah. I think what would be an important next step is like right now we’re assuming and I mentioned that in the presentation that peripheral insulin resistance occurs in parallel with brain insulin resistance, but there might be credations in dominance of one or the other. And I think that would be very interesting to figure that out if it really develops synchronized or the one weighs heavier than the other. And so I think for that, for example, I would like to be able to do clamps in the scanner and look at both periphery and brain at the same time.

Speaker 2 • 49:30
And then maybe to come a bit to the hype of the GLP-1s and a lot of attention has been devoted to the foot noise. Do you think that there is a link or how do you see the link between the reduction of the food noise that these patients experience on treatments?

Speaker 3 • 49:53
– Interesting question. So I think the food noise definitely plays a huge role because our brain reward system is just basically made made to react to that and make us want things. And I think the reduction in food noise is a tremendous help with reducing that. However, I gotta think, but I’m not really aware of, I think those studies are just in the process because I think there is a lot more work that should be done on the double, triple agonists and brain reward activity. I don’t think there’s enough out there yet.

Speaker 1 • 50:59
And perhaps a last question for you, Tanja, but do you think that the brain imaging could be a good way to phenotype patients who are non-responder to the anti-obesity medication we have today to see what can be possible way to help those people who do not respond?

Speaker 3 • 51:26
Definitely. Yeah. I think that would add another piece of the puzzle to explore that. Because like in the end, the whole weight balance is regulated in the brain. And I think that is an important aspect of this. And I think it’s expensive, it’s non-invasive, but it’s still very strenuous for the research participant. Not everybody wants to be in a scanner. So the experiments are fairly scarce and the effort is big, but I think that would be an important, I think that would be adding an important part of the puzzle for phenotyping, yeah.

Speaker 2 • 52:24
– Okay, thank you, Tanya, for your excellent presentation and the discussion. On behalf of our Belgian organization, we really want to thank you.

Speaker 4 • 52:34
We also want to thank all of the participants for joining and I wish you all a very wonderful evening. Bye.