AI Discovers Next Gen Obesity Meds

[00:00:02]The next obesity drug war may not be Lily versus Novo Nordisk that we've talked about basically for the last three and a half years. It may be humans versus AI because a Chinese biotech company, Athletus, you heard me right, is a Chinese biotech company uh that says that they've used an AI drug discovery platform to design two new obesity drugs that could be dosed as little as once every three months. We know how that's gone so far.

[00:00:30]I guess TBD and one of them reportedly outperformed the combination of turside and auroral lintide in obese rats.

[00:00:39]Something we've talked about a ton here at on the pen. Now, before anybody gets too excited, this is not maybe what it all sounds like on the surface or in the headlines, but this AI story might be much bigger than the actual drug story itself. That's what we're going to get into on today's episode of On the Pen Live. Welcome back, my friends.

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[00:01:43]Welcome to On the Pen Live.

[00:01:48]Welcome back to On the Pen Live. I'm your host Dave Napman on the major.

[00:01:52]That's why I'm here. You are on the pen.

[00:01:54]We go saxenda vtosa trudicity majors atbound compound that pen is what we talk about each and every day here Monday Wednesdays Fridays we're live on YouTube on X on LinkedIn and it's so good to be with you so if you're just tuning into this video you saw the you saw the thumbnail you're like this is really cool why does this guy take so long to get to the point it's because this is a live show it's a live show so we do this for an hour every Monday Wednesday Friday so hit the subscribe button join us every Monday, Wednesday, Friday live at 11 a.m. Central. We'd love to have you here as part of our community. Uh Mindy, Ruben, Jude, I see you. Amy, Joe's in the house. Thelma's in the house. Good to have you here. Ray is here, too, gracing us with his presence. So good to be with you all on a Monday and to bring you a very exciting story. So, Asthletus Pharma.

[00:02:42]So, you you're hearing me right. Right.

[00:02:44]I'm saying as lettuce, it's not exactly how it sounds to the ears. It's spelled as C L T I S. And no, athletus is not how we got cycllosporasis.

[00:02:56]It is an actual biotech company out of China and listed in Hong Kong. They submitted two IND applications to the FDA. That's basically two two new drugs that they want to run clinical trials on. And the um the fact of the matter is that these medications have only been studied in in animals so far, but they were discovered by an AI drug discovery platform. And the cool thing about this, obviously this is all pre-clinical. It's this is rats. Doing this stuff in rats is a lot easier than doing it in humans, especially when we talk about the the longer dosing, right?

[00:03:36]But one of the things that's very exciting about this is that these were discovered by an AI drug discovery platform. And if that proves to be viable, we could improve upon some of the molecules and the receptors that we have currently in pretty massive ways, which is very exciting. So, the first one that I want to talk about, uh, and we're going to have a full show today.

[00:03:59]We got hamone coming in later on. Make sure you hit the like button, hit the subscribe button down, hit the hit all the buttons down below. That helps other people uh get access to this content as well. Helps train the algorithm. Um so let's talk about ASC for athletus 36. Uh so this is a peptide amaline receptor agonist. It's been developed uh for once monthly and potentially once quarterly dosing. Now we've seen this in multiple other drug formats. So it's not like AI came up with this novel idea. What if it lasted longer? What if we could dose it less frequently? This is obviously something that humans have come up with without using AI drug discovery platforms. We could talk about meta which was acquired by fizer and their long acting amalin and their long acting GLP1. We got some data just back a couple of weeks ago at ADA the American Diabetes Association on how those are sort of panning out in clinical trials.

[00:04:52]We could also talk about Merit, which is a long-acting GLP-1 and GIP1 antagonist uh from a company called uh Amgen. And Amgen uh is testing maritide and and they were looking at even up to six months dosing at one point. But what they found is that it's very hard to tolerate a drug when it's got such a long halflife, right? if you're going to have side effects. People don't generally want to get stuck with the side effects of a GLP-1 for a month before those really start to subside.

[00:05:23]And so that is what's been really challenging for these companies to manage. where AI comes in and where I get excited about this is is that AI can find out uh the holes so to speak in some of these other molecules that make it less uh less tolerable for patients or or perhaps increase the efficacy without dialing up the side effects. AI can just do a lot a lot quicker than humans can.

[00:05:50]It doesn't mean that humans aren't involved in the process at all. Of course they are. It's humans working with these learning machines. But uh that is sort of the story because people are like well this isn't new receptors.

[00:06:01]Uh amalain has been around before and as we'll learn about ASC 3635 as a combination uh but I digress. So the company says that this formulation uh was able to create a much longer half-life than a laurelin tide and obviously kagrillinide which will be first to market as an a long acting amalin. uh long acting by long acting I mean about a week long uh halflife for kagrillin tide I think it's 15 days for a laurel lintide so expanding upon even that is pretty incredible asthletus claims that asc 36 produced greater relative weight reduction than prolinitide andoralide in obese rat studies and I think it was up to 51% greater than the trespide and and um auroralide combination for the next one that we're going to talk about which is a combination of this drug and another. So imagine moving from your weekly injections uh or possibly uh to to something that's possibly like four shots a year. Um so when we talk about adherence to the drug, this is something that these drug companies are always trying to solve for. Now I know from the patient perspective, we go, do we really want to get stuck with those side effects for that long? And I think that's where the rub comes and that's where the clinical trials will bear this out. But what's very interesting to me more than just this this standalone amalin long acting amalin is this ASC 3635. So we just talked about ASC 36 this combines it with another molecule 35 35 ASC35 targets GLP1 and GIP. So they're coming up essentially with a triple agonist lost my microphone. Um they're coming up with a triple agonist ASC 3635 which targets GLP-1 GIP and AMOLIN and together um this goal is a once monthly injection that would be a essentially triple agonist right instead of redatide this gives us GLP-1 GIP and glucagon this gives us GLP-1 GIP and amalin we're seeing more of these combination therapies uh and and so this is obviously very intriguing not not because it's the first of its We see other companies that are that are looking at uh for for an example, Novo has one pretty far along, a GLP-1, GIP, and in Amalin, I believe. If I'm not speaking out of turn, I believe we've covered that before. Um I believe there's even another company or two that maybe have something similar, but again with the AI drug discovery, they're looking at um you know, potentially ways to improve upon some of the things that the other companies are doing, including it being like a once monthly injection.

[00:08:30]So, this is uh pretty exciting. So Athleta says ASC 3635 the combination appro produced approximately 51% greater relative body weight reduction than aurora lintide and tresepatide did in obese rats. Now we know that that we've seen human data now on aurora lintide tzepide. It's going to be a blockbuster in its own right because we see patients losing a tremendous amount of their body weight. Even with the laura lintide alone uh it's pretty close to trespatide in its effect efficacy and then when you combine those I think we're going to see reatrite or greater level weight loss results without the massive uh spike in in uh heart rate and so that is pretty exciting. Uh again there they would be able to accomplish this um in in a much uh less frequent dose as well which is really exciting.

[00:09:24]And the interesting thing about uh amalin is they tend to not come with all of the side effects that you see with other incretin medicines like GLP1s and GIP. So we'll have to see how this pans out because again this is preclinical animal data uh and we'll need human trials to prove this. That's basically the story here that the FDA is now uh considering approving these IND applications for Slettus um which were again both discovered by AI assisted uh drug discovery platform that they have there. Um they're leveraging basically AI to help identify and optimize obesity drug can this would be a huge test of whether or not AI designed obesity medications could ultimately enter the market and be a big contender for the future of obesity medicine. I think they will be. Uh so can it improve upon the speed, the quality, the selectivity and durability of of drugs that are currently on the market is the real story. So two new molecules, very interesting. We know that Lily and Novo have both invested quite a bit in AI.

[00:10:28]They're a little less bullish maybe than Athletus is. So Athletus is putting this out here. Um they're they're excited about it. I'm not sure that Lily and Novo are really flinching uh with this information here today, but uh it's interesting for patients nonetheless.

[00:10:44]So, that's what we wanted to bring you today. Now, I want to do a little check-in here. By the way, we did get to 30,000 on our Instagram account. Uh so, thank you for helping us to get to 30,000. Ne next next goal is to get to 33,000 and have more subscribers officially on Instagram than we do on on YouTube. YouTube's slow growing here for the last year and a half. If you're new and you're listening to this program today, what my ask is that you would simply hit the subscribe button. That really helps uh the work that we do here on YouTube because we put the mo majority of our effort goes into these YouTube videos. We're live Monday, Wednesday, Friday at 11 a.m. We drop a podcast every Tuesday uh as well, which is the not live video. And we put a bunch of shorts out that in fact, we put a short out on this topic this weekend. So, if you followed us already, you may have already seen this information. and uh you would have had that prior too. So that's that's the story here with athletus. Pretty interesting. I think uh fewer injections uh is an interesting thought especially like for somebody like me. So I think about the fact that now I'm I'm actually injecting uh tepatide a couple times a week. Tzepide has a very short half-life. It's only 5 days. So if you've ever taken Tzepide and you thought, you know, man, I don't really feel much after a couple of days. That's because it reaches the max uh serum level pretty quickly within, you know, for I think for me it's within 24 hours, but I think the the window average is from 8 to 72 hours. So, you're going to fall somewhere in there where you're going to peak at at your serum levels of tzepide. And so, a lot of people benefit from dosing a couple of times a week. I do that, but then I'm also pinning other peptides. I'm taking tessimorellin, eparlin, matsi. Um I'm taking every other day I take a testosterone injection. And so like I'm just doing a lot of injections. And so the thought of maybe having one that has a more steady um concentration in the blood, a steady rise and and not this huge peak and this huge crash like tepatide does is rather pretty intriguing because I'm getting kind of sick of poking my body constantly. And uh there are concerns that are raised with with doing you know so many injections uh if you're not moving around. Thankfully I got a lot of surface area to work with. So, we take advantage of that. But longer dosing intervals may provide better adherence to these medications. We also hear about a lot of folks who give up on these medications for one reason or the other.

[00:13:10]Um, this may help again get that level out that peak in that trough. If we can do that effectively with these longer dosing and we can actually get rid of some of the side effects, uh, then I think that will improve adherence to these medications. A lot of folks, believe it or not, don't give these medications long enough to work because they either get the wrong dosing uh or they're not just given very good guidance on how to use these medications. And so, I think it'll be very interesting to see how these play out. Uh more drug classes may also create better better options for people who don't respond to current therapy. So just while we're not seeing anything novel in terms of the targets of the receptors that these new drugs are hitting um I think eventually we may we may see combinations that we don't see um you know just a team of scientists coming up with and and so that would be exciting too and so these AI molecules could potentially allow for more personalized treatment which I think this all is headed towards a much more personalized approach to obesity much much more similar to the way you see cancer treated right there's there's genetic markers involved there are a whole a lot of variables that are considered with cancer that we've yet to consider with obesity that I think ultimately we will because we know it's chronic, but we also know it's multiffactorial. It can include genetics. It can include environment. It can include mental health. There are so many factors that contribute to obesity.

[00:14:27]Uh that I think ultimately it deserves to be treated with that that kind of um that kind of personalized target and I think that AI may help us get there.

[00:14:35]Ruben says, "Does a blood test tell you if the epramarlin and testin are working?" Um yeah, you can you can actually uh have a blood test done called your IGF-1 levels. And so your IGF-1 is basically the hormone that uh epipamelan and tesamelanin are are signaling your body, your pituitary gland to make. Uh so you can and probably should get your IGF-1 levels checked before going on a peptide like that. Uh a growth hormone secret uh like like tessillin or epomelone and then find out after you've been using it for a couple months what you're seeing. um the source for the the peptide company that I use. Yeah, no problem. So, I I use a company called Voit. They are the sponsor of our podcast and Voit um prescribed these and so these uh are coming from licensed uh compoundies. A lot of people are like, "What's the legality there?" I don't really care. um if compoundies are offering it um it's coming from a compound pharmacy that is subject to um to you know inspections and they're sub subject like so I don't know what the law is. I'm not a lawyer. Uh but I know that if I were a doctor I would feel an obligation to prescribe anything that I thought could help a patient who needed it. And for me what uh my story has been is uh I got medication through a traditional doctor for the first couple of years I was on a GLP1 with very limited guidance on them. Now granted, they were new medications, but at the same time, yeah, you can contact them by going to my link tree. You go to go to otplinks.com uh or you can go to voafit.comotp.

[00:16:08]Uh maybe Hamone can put voafit.comotp in the chat. Uh but you go to otpinks.com and it's there's a whole link there. Uh, but if I were a doctor and I were prescribing, I would feel an obligation if it was available from a compound pharmacy to give my patient anything that I trusted a source of uh, and and that could help them metabolically. And my story is that after receiving the drug for a couple years through traditional channels and not receiving very much support behind it, uh, I maxed out at the 15 milligram dose within a couple of months of being on the medication and then I didn't lose any more weight. It it didn't assist me in the way that I needed to. In fact, I developed anhidonia because of the high levels of the drug. Uh, so right now I am at 269 pounds as of this morning, which is just a couple of pounds off of my lowest weight on a GLP1, and I'm using onethird of the dose of GLP of of Zep Bounterside that I was using prior to. Uh, and I've I've gotten similar results, but again, I'm using other other drugs to address my my metabolic health. Mi um uh a tesmearillan epipamearellin I'm using uh treating my finally treating my low testosterone which I had never had checked before it was in the 200s and I found oh wow my testosterone is incredibly low so it's funny you start to address a patient more holistically and then ultimately what happens is is you know people respond better and so we don't have to redline what I always talk about is that we don't have to redline one single pathway like we don't have to redline the incrretin path pathway at the highest doses we can address the inkin pathway which really helps to treat even at a low dose tzepide does wonders for my blood sugar I don't need 15 milligrams of tzepide and I don't think most type two diabetics that I've met do um most type two diabetics respond to that 2.5 milligram dose of tzepatide pretty well to to their blood sugars now this is not medical advice I'm not a medical doctor I'm just a guy who covers this stuff on the internet but but I would say you know for me my my diabetes is controlled really well at at those low levels and I didn't really get a lot of benefit going up to the 15.

[00:18:15]That's not to say that people won't. Of course, the clinical trials of surmount data tends to show that it's dose dependent in terms of the weight loss that you're going to experience. But I think in the real world these drugs work a lot differently. Uh and in the real world uh things tend to play out differently uh for for each individual.

[00:18:33]So I think the point is get go somewhere where you're treated as an individual, not a number. And I think that if you are able to do that um you are very fortunate and um I use I use a company called Voit and the doctors there prescribe I don't have I don't take anything that hasn't been prescribed uh to me and and offered through a licensed compound pharmacy if that help helps you. So yeah hopefully that's helpful. I I appreciate the question. Uh Mike Trenchetella says, "Tessamelan is the goat uh growth growth hormone releasing hormone." Uh that's right. That's what we uh that's what we have in tessamellin. Uh again, I always like to think about it is your pituitary gland releases IGF-1, growth hormone, right? And tesarellin sort of pings that pituitary gland to release it. So it's almost like dialing into a radio station, right? But when you combine it with the peptide epimelan, epipomelanin is going to increase the volume right the intensity.

[00:19:35]So th those two work sort of synergistically. One to dial in the frequency so that your body is releasing growth hormone effectively. Uh you often take it at night which is when your body would naturally release growth hormone.

[00:19:47]Um and then ultimately uh the epomellin combination will allow that intensity to increase. Now, one of the things I've got this fly that is insistent on driving me nuts this morning. Uh, one of the things that's interesting about this combination is is that IGF-1, the growth hormone, it really seems to target and prefer uh eliminating visceral fat. So, so one of the main benefits of testomone and you might be like, well, this is just peptide nonsense. actually uh testosterone has been proven in the HIV population at least which probably would would extrapolate to um to the general population in terms of visceral fat like they they tend to accumulate more visceral fat and it's more problematic for them uh it affects their their their mortality uh at a to a higher degree and so a grifta which is tessamellin an FDA approved therapy was approved for the reduction of visceral fat in HIV patients so this is not like this is lots of human studies to a lesser extent. Uh but but these uh these are hormones that that are are very helpful uh have been very helpful for me in terms of reducing that visceral fat. And so again, you address multiple pathways uh instead of just redlining the one pathway and being so hyperfocused on GLP1 or GLP1 and GIP. I'm gonna scroll back up. I know Hawkeye girl says, "Thanks.

[00:21:13]Great. Great job, Dave. Thank you.

[00:21:16]Um, I know you said, "I'm currently cooking the crud out of my veggies on the stove. I'd like to stay away from parasites." Yes, no kidding. Ask lettuce, we call it. Um, let's see here.

[00:21:28]Mike says, "I've been working with Justin Morland for many, many, many, many, many years with clients and even business colleagues and family and even own my own personal experience. Give it about six to eight weeks." Yes. Um, for me, uh, my my body composition scale shows that I've I've really gotten rid of most of my visceral fat, uh, using Tesmearellin. So, I'm very thankful for that because the visceral fat is the kind that kills you early. I mean, it's just there's no better way to say it. If if a drug can target visceral fat, you're you're likely going to improve uh the length of your life by reducing your visceral fat first because that is the fat again that accumulates around your organs. It's very dangerous to live with a high level of visceral fat. Um, and so I think ultimately we'll see that that uh drugs like reatride uh help with that visceral fat too. Um, I think we'll see studies come out about that. I'm sure that um some of these studies are using I know some of these studies are using DEXA scan. Some of them are even using MRI and ultimately we'll probably be able to prove that that these new generation of GLPS really help to target that. We'll have to see. New generation of nutrient stimulated hormone drugs is probably better way to say it. Uh let's see. Big Rigo says I should consider Tessa but already on tur and NAD plus soon. Clo maybe Cardilax. I will be a pin cushion. That's sort of how I feel right now.

[00:22:48]Uh cook parasites to add protein intake.

[00:22:51]That's right.

[00:22:54]Is everybody How's everybody feeling?

[00:22:55]Has anybody had uh dealings with this cycllospor cycllosporasis?

[00:23:01]Uh I hope not. I hope that you're all healthy and and feeling well. We're 23 minutes into this live stream. I hope that you are enjoying it uh on this Monday. Now, my first ask of you would be that if you're not subscribed, please hit the subscribe button. We bring you obesity medicine news from the patient perspective that empowers you to have better conversations with your doctor.

[00:23:22]But subscribe if you've watched this far and you've enjoyed it. Subscribe. That's that's all we ask. And then hit the thumbs up button. All that stuff helps to uh push this out to the algorithm.

[00:23:33]And it also helps us to measure like is is what we're doing providing value because this is a big thing to prepare for three days a week. Um are we you is it the best use of our time, my time, Handbones time, the community's time. um your feedback helps us to gauge whether whether or not that's the case. And we measure that oftentimes in likes, comments, and engagement. And so for better or for worse, that's sort of how how we measure uh how effective the work that we're doing is or whether it should be uh better served somewhere else. So uh appreciate everyone who who uh engages with our content every day. With that said, we're 24 minutes into this live stream. We got Hambone waiting on deck waiting in the wings. Uh, so we'll bring Hambone on from her remote location. Hamone, welcome to the stream.

[00:24:21]>> Hi guys, my remote remote location. Uh, I'm so tired today. I knew I was going to just be foot in the mouth as soon as I came on. Here I am. Um, I'm actually still in New York um through Wednesday.

[00:24:38]So, uh, coming to you live from my friend's house and she's an actor. So again, I have great lighting and a great background today. So good to be here.

[00:24:49]>> Compliments of Ann's actor friend.

[00:24:52]>> Yeah. Um, as much as I don't want to admit it, it's kind of the work that I do. Dave, I'm kind of worried I might have gotten that bug that you were just asking everybody if they have cyclloppploren.

[00:25:07]>> Cycllosporiasis.

[00:25:09]>> Thank you. Yeah, I've been traveling a lot, you know, um uh as a lot of you know, I live uh back and forth between Iowa and Indiana most of the time and but I've been traveling so much and you know, you have to eat on the run. You can't prepare your own food a lot of the time.

[00:25:26]So, I'm I'm I guess I'll get a test and I'll let everybody know.

[00:25:35]But, uh yeah.

[00:25:36]>> Do they have a test for it? Uh, from what I read, yes, you can only identify it through a stool sample. So, I'm going to have to go do that. Um, because I'm on great probiotics. I'm eating really well, generally, just very healthy, and I just, you know, haven't been the same for the last week or two. So, no fun. But I got to figure that out because a lot of you know I'm headed to Spain here in a couple weeks and I'm like I don't want to be dealing with that.

[00:26:10]>> How long do you know how long it lasts if you can track this thing?

[00:26:14]>> Well, uh what I've been reading has been because I haven't done a deep dive on it, but a doctor that I follow was saying that you have to you have to identify it through a stool sample and that the symptoms can come and go and that's why it's hard to identify. And then um uh a big New York magazine or New York Times article like they had two different Instagram posts and it was it was disagreeing with that essentially saying that it can eventually fade out.

[00:26:46]Um, but I think there's probably just some nuance there that the doctor is hitting on that, you know, it may you may seem like it's gone and it may be it may come back so infrequently and inconsistently that you may just not know that you have it or you can live fine with that. But, um, I would love to have my gut flora be nice and balanced.

[00:27:09]So, I'm probably going to do that when I get home. So, >> yikes. So, so Google um AI says that without treatment, cycllosporasis symptoms can last anywhere from a few days to a month or longer.

[00:27:22]>> Yeah.

[00:27:22]>> The illness frequently occurs in waves where symptoms seem to clear up before returning with a prescribed antibiotic like trimethoprime sulfamethoxazol.

[00:27:33]Most people feel better within a week or two. If your symptoms are severe persistent, it's highly recommended to consult a healthc care provider for an official diagnosis as treatment may require prescription antibiotics.

[00:27:43]>> Yeah. Yep. I took a screenshot of that the what that doctor had posted. So that is that is the drug that I'm hearing about. But um >> yeah, I need to go read this study.

[00:27:57]>> Oh yeah. Yeah. Uh Debbie says they're also saying that it thrives in heat, so it should die down after the summer.

[00:28:03]Yeah. where what like where does this come from? And I mean I'm asking this sort of rhetorically like where does this thing come from and why isn't this something like I I know back when I worked at Olive Garden so uh where all all roads lead back to Olive Garden. I remember there was an outbreak in Indiana of uh norovirus. Now, neurovirus is is sort of one of those um highly communicable um u similar sort of diseases, right?

[00:28:32]Where you you can contract it. It's horrible. Vomiting, diarrhea, uh and just just disgustingly contagious. Um I'm just in this day and age, I'm just shocked that we don't have more of these types of like stomach bug outbreaks because there's so I mean even like you just think about travel. I think about when we traveled to Florida at the beginning of the month, the we were in the O'Hare airport and I can't remember what was going on particularly uh but the the TSA lines were insane.

[00:29:07]>> I mean just insane. In fact, it was kind of scary how fast they were pushing pushing uh passengers through the TSA line uh because you know it was just like not very thorough. like it was so fast and it because it had to be otherwise you would bring tra airline travel to a grinding halt. Um but you just think about the surfaces alone in an airport. Um and then I always I have this whole comedy bit that I've been working in work I've been workshopping a bit now. I've been like I've been thinking about this bit about because it's astounding to me when you go through the O'Hare airport like if you just think about sanitation like because I'm somebody who thinks about this a lot when I travel I'm just very grossed out when I stay in hotels I'm very grossed out to be in an airplane it just the whole thing gives me the complete heebie-jebies and one of the things that you think about is when you go to the O'Hare airport I don't know if you all have ever looked but if you've been through the O'Hare airport the toilet toilet paper. This is probably the second or third time I've talked about this. The the toilet paper is like, first of all, it's very narrow, right?

[00:30:14]So, it's like they've shrunk it down in coverage, >> but you can see your hand through the other side.

[00:30:22]>> Yeah.

[00:30:22]>> And I'm like, this is the most unhygienic toilet paper that I've ever seen in my life. And you think about all of the people using the restroom in the O'Hare airport and then >> they're just using more. It never makes sense to me. Just, you know.

[00:30:38]>> Yes. Yeah.

[00:30:39]>> Use higher quality people.

[00:30:41]>> When you get to one of those rolls of toilet paper, you're doing one of these numbers.

[00:30:45]>> Yeah.

[00:30:47]>> Until you got about eight feet of toilet paper and then Yeah. So, anyways, >> grandpa would be appalled. I remember our grandpa would coach us. He would say like two or three squares. Remember that, Dave? When we'd be at the cabin?

[00:31:01]>> Yes. And the door to our bathroom in our cabin because it was so unfinished was like a flag.

[00:31:07]>> Mindy said she just came back from O'Hare yesterday. Dave is right. There's like I'm a huge Chicago Cubs fan. Um like huge diehard Cubs fan, huge Bears fan. But the city of Chicago in that airport, that airport just needs to go away. They just need to they just need to burn it to the ground and start over.

[00:31:28]It's such a gross airport.

[00:31:29]>> Oh boy. Uh, I could I could just like I literally could go on the road with my O'Hare.

[00:31:35]>> Yeah. Yeah. I've always got my sanitizer kit. You know, I'm wiping down the surfaces. I always wear a long sleeve even if it's just like hung over my arms because I don't want my skin to touch the seats. That's usually because of the flame retardants that they have to just spray everything with and it just >> Oh, yeah.

[00:31:52]>> And then if you fly in this So, so this is like adjacent to what we normally talk about, right?

[00:31:58]because this none of this stuff is good for you, right? I guess you could argue that a trip to O'Hare is going to help build up your immunity. But when you're sitting on an airplane in the wintertime, because I used to travel all the time for work, like probably was gone about a month, a week out of every month for 10 years. Um, and when you sit on an airplane in the wintertime and they put that deicer stuff on it, >> Yeah. Who knows what that's made of, but the whole cabin smells like >> whatever that is. And there's no way that's going to >> on top of the fuel exhaust. Yeah.

[00:32:32]>> Yes. And then just the generally just the recycled farty air, you know, like I call I call an airplane a giant fart tube.

[00:32:41]>> During co they were actually touting that the air quality was safer because they do circulate it so quickly, but it's full. It's constantly getting a new pump of chemicals from either the fuel or the deicer. So, um, but yeah, >> that's when I like to wear a mask just to keep the particles out.

[00:33:05]>> The farticles.

[00:33:08]>> So, all right. So, that was a that was a rabbit trail. What I know that you've got stuff other than the toilet paper at O'Hare for us.

[00:33:16]>> I do. And other than my tummy troubles ti that you're feeling bad. So, very appropriate for that topic today. Um, yeah, I was looking at another study uh and continuing this uh kind of theme that I have going about exercise and obesogenic environment and just the the little efforts that we can put in that actually make a huge impact and that we need to really take seriously and to also help motivate us. Um, and this is another one about exercise. Um, it was a high quality study. It's called, it's got a very scientific um, title, but and I did add the studies on the last video on the last live that I referenced. It's in the description. If you want to go find it, I'll do the same thing today.

[00:34:07]I'll link this um, PubMed article and the whole article is available which is great. But exercise induced activation of ventromedial hypothalic stereogenic I think I said that right factor one neurons mediate improvements in endurance. So essentially a very scientific way to say that um they're looking at how your neurons so how your brain is really playing a factor or not in your ability to build endurance.

[00:34:44]>> Um so it was really high quality mechanistic neuroscience study. Um and it shifts our understanding of exercise adaptation. So um so there might be specific neurons required um for endurance and metabolic benefits.

[00:35:03]Uh, and this was a a my study, but I really love it because I think it's going to be very helpful for practical life improvement, but also another champion of of um taking away the stigma of why people have a harder time getting into the routine of working out. Um, and we've already stacked so many things on top of that, including the topic of the memory that our cells hold about our baseline weight. You know, your your cells 10 years out still are holding on to that >> whatever level of obesity that you came from. But this one I I another personal reason why I find it interesting is that my husband growing up was an athlete. Um he's 67 and uh he played basketball and and um tennis and and he was always very fit obviously. Um he didn't get made fun of for being obese, he got made fun of for being a thin person because he just couldn't keep any weight on. Um and so he was very athletic, very lean his whole life until probably his late 20s, early 30s. and um he just uh got back into exercising more consistently and he's running and the way that he's just put on muscle in his legs has been very noticeable, very quick, very defined. Um and so we were having this conversation about how his body just, you know, remembers. He's got this muscle memory.

[00:36:50]Um, and you know, I've heard that bandied about, but I didn't really understand any real true science to back that up. Um, uh, but I I I've heard a lot about it. So, I wanted to look at this study. And the question that the researchers were asking was, um, for decades, we've assumed that endurance improves mainly because of your your muscles get stronger, your heart pumps better, lung lungs become more efficient. Um, but they wanted to ask, could the brain actually be the thing that tells the body how much it's allowed to adapt to exercise? Um, and I've I've also heard another thing thrown around about just women in general. You know, usually it's a joke, but you know, some people really do think it just that that that women a lot of times have a uh harder time getting over I'm I'm forgetting what people are actually saying, but like you know, getting over that hump of of initial exercise, that exercise resistance, which we know now is related to metabolic things and PMOS.

[00:37:54]So there's a lot of layers there to unpack, but um but this basic neuroscience animal study. So re researchers used genetically engineered mice um and they did like treadmill exercise training. I want to I wish I had some clips of this, but brain imaging recordings of individual neurons. There's a lot more detail in there. Um muscle analysis. You can go read it for yourself if you want the nitty-gritty details, but um but this was not a human study. So um and the neurons that were studied they focused on these this small population called SF1 neurons um and for you scienceincclined people that's located in the vententral medial hypothalamus.

[00:38:35]So um and this this area is known for uh its role in energy balance, blood sugar regulation, uh metabolism, exercise responses and body weight. So the question was whether these neurons are actually necessary for exercise adaptation. Um and the main findings were exercise activated these brain neurons. Um even after like a single bout of exercise um and after repeated training so even more neurons became active um and they were easier to activate. So um so that's like an example of brain plastic plasticity. um the brain itself adapts to repeated exercise. So um they also found that the brain remembered previous exercise, so more um connections, stronger signaling, increased neuron excitability.

[00:39:32]Um and then the authors were suggesting that the brain develops a kind of exercise memory that helps future training sessions produce greater benefits. So that that's was really interesting to me, especially when I think about the people in my life that are just like unbelievable machines and they have great capacity when it comes to exercise. And it just it it feels to me in my observation that they just hit a different level and there's this and I feel like I've experienced just a little bit of it where you just start to the rhythm and the joy and the you feel good doing it. you want to there's a level of wanting to do it that shifts when you break through a certain level and so I was like I wonder if this study can explain some of that and I feel like it is um so turning these neurons off prevented normal training ad adaptations so prevented normal training ad adaptations um and that's probably the biggest finding uh that when they blocked that specific neuron activity um after exercise the mice failed to develop many of the normal adapt ations that we we just mentioned. Um so the metabolic improvements, muscle remodeling, um and despite performing the exercise, which is crazy to me. Um so turning on these neurons increased endurance gains um and improved uh improved overall performance. Um, so it doesn't mean the study doesn't necessarily mean that your brain quits before your body because that was a question that I don't know that was the intuitive question that I had had about this. So um you know like when you think about just when we talk about having the right mindset and having the right um thinking the thoughts that help motivate you or set you up for success. This is different than that. This is this is down to a neuron a cellular level um beyond attitude and perspective. Um this is are your neurons firing? Um it also doesn't prove that fatigue is all in your head essentially. So um muscles cardiovascular function, mitochondria, fuel stores and oxygen delivery remains essential. Um so the study I think suggests that the brain is an important regulator of how the body adapts after exercise but not the sole determinant of effort. So um and again a limitations because it was a mouse study um and our brains are similar but not identical.

[00:42:13]Um, so it'd be really interesting to see some human studies, especially because this was highly specialized methods. Um, and they focused specifically just on endurance and they used artificial stimulation, you know, to shut those off and turn them on. Um, so, you know, suggesting that we might be able to do replicate that at home with supplements or meditation or cold plunge, um, is is very would be very speculative. So um and there's no direct uh obesity or GLP-1 population obviously in this study. Um uh >> yeah and I was just going to say like from the other perspective you're looking at it so basically you're coming at it from the perspective of saying like essentially when you are exercising when you are building muscle that your body remembers that essentially and the the inverse of that is is also true because what we know about fat tissue and fat cells like when you when you become obese uh your body is in an obesogenic state you can lose the weight but you don't lose the fat cells, they shrink. And so you're living continuing to live with these fat cells, which they've shown can even after weight loss for up to I think it was seven years, maybe it was 12 years.

[00:43:31]>> I got 10.

[00:43:32]>> I'm I'm going off of memory here. So, but however long it is, those so cells are still pinging your brain the same way, saying like, "Hey, we're ready to receive energy. We're ready to fill back up. Um, give us energy." Um, and so you've got like this biology that's sort of working against you if you're living with obesity. And so you kind of have these two competing forces. Um, and and also like with those fat cells come inflammation and changing in hormones and cytoines they release. Which is why um, you know, when you talk about how how exercise and the building of muscle can make your body better using glucose, your mitochondria become more efficient.

[00:44:15]your body sort of adapts in this really positive direction. Um, obesity creates its own biological memory too, which to tie it back to earlier when when folks were asking me like where do I get my peptides? Why am I on certain peptides?

[00:44:27]Like when you think about, you know, all your total biology, right? You've got the obesity is is fighting against your body in so many in so many ways. um from a hormonal and signaling standpoint to a a um inflammatory standpoint. Um and so you have to address it from multiple angles for for a lot of people. And then even when you get to if you're somebody who's listening and you've been on a GLP1 and you've got to your goal weight uh and you're like, "Can I come off this medication?" Well, just know that the the fat cells have shrunk, but they're still there, and you still have are likely going to have biology that's working against you to drive you back into that obesogenic state, which is why >> it's worthy of continued treatment, whatever that whatever that treatment looks like. I'm not posing that it has to be the same drug or even a drug for everyone, but I think uh treatment is is going to be something that is is long-term and you have to think of it um you have to think of it long term and not just like I'm going to use a med.

[00:45:31]I'm going to get to my goal and then I'm done. If you're truly living with obesity, you're truly working uh against your biology to to kind of overcome that that state of overweight. So >> acknowledging and validating the stack that is against you that still remains once you have come down to a weight that you are happy and healthy with. It's it's so important and also and then that the people around you know that you are still battling that you are not you know you're not just working from the baseline of your current weight. you have complexity in you that you have to remember that you are dealing with, >> right? Which which is why eat less, move more is such a um such a worn out phrase because there's so much more nuance than just doing that.

[00:46:25]>> Um I think that um >> uh Debbie touched on something too that I thought was interesting. She said, "I've never experienced joy from exercise." Um, and I think like that's that's very like I would maybe say something similar like not intentional exercise like not the kind where you go and run on a treadmill or that you go and push weights. I think I have felt a sense of accomplishment.

[00:46:47]>> Yeah.

[00:46:47]>> Um, from doing those things. But I don't know that I've ever spel I've ever felt joy or anticipated it in a way that I was like, "Yay, I get to go work out." I mean, some of that you can probably do some mind work on, but I think uh what would you say to somebody who um who sort of feels that way towards >> uh towards exercise and movement? I know what I would say, but what would you say?

[00:47:11]>> Um somebody who hasn't felt that joy from >> Yeah. Like in other words, you don't have the benefit of your your your body sort of pulling you back towards >> Yeah. something that once gave you something, right?

[00:47:27]>> Yeah. Um I would say that it's just a validation that you are up against more than the person who is experiencing that and and don't be invalidated by people who just want to tell you little quippy things that you know you should get you there. Um they they don't know what it's like to be in your genetics and your body. And what I love about this study is that there it does bring hope into the picture as well because it the takeaways are really that exercise is teaching your brain and consistency matters more than perfection and that can be a huge huge barrier to entry for people. Um and that early workouts will feel very disproportionately hard.

[00:48:16]>> Um and that's and that's science. Um, and there's bi there's biological explanations for why endurance often improves with repetition and your central nervous system is adapting, not just your muscles. And then if you tie that into everything else we've been talking about, how uh uh at our last live, the nervous system was the biggest signal between the gut and the brain.

[00:48:41]And so if you're dealing with a nervous system that has issues, whether from, you know, traumatic life experiences or imbalances in your body, all of those things are stacking to a very disproportionately hard uh entry into exercise. And then you're you're looking at these people who have hit another level where they're literally feeling joy and bliss from running.

[00:49:08]and they think that they can just say, "No, you just need to run a few more laps and you'll hit that bliss." That's not how it works. That's not how it works. And and also there's another piece of this puzzle um if you go read the study that that really validates that recovery is really important. And I I feel like my husband is such an intense like go go go person execution whether whatever stage he's at. It's just how he's specifically wired and that he has it's been a long journey to embrace recovery and how that looks different for people from person to person. So um >> so so that getting good recovery can drive adaptation of those neurons. Um, so that's another thing and that might look different for you and that's also why we say talk to your medical providing team or your trainers and figure out what that looks like for you and take it really seriously. Uh, that what what's going to work for you is not going to work for the next person. Um, and really really try to shut out the voices that are going to push you away from whatever is moving you forward.

[00:50:18]>> Right. Right. It's great. I think when I when I think first of all Chris uh said you work out because you have to and are overweight, not because you like it.

[00:50:29]It's not about how you feel about it's about understanding there's a problem and you need to fix it. I think that's fair, but I think it's also I think it's also avoiding the nuance of of the challenge that it is for some people.

[00:50:41]And so when when I talk about embracing embracing that challenge, what does that look like? how if I don't have that drive like I think about this is a perfect example right my friend Ike who I've been working out with we've taken a few weeks off uh for the summertime but who I was working out so Ike has played football at a professional level for the last 10 years of his life he played uh at a high level in college for the state of the university of Iowa and before that he was a stud athlete in high school all of his core memories of growing up were in the gym hitting PR s with his buddies. Um like like there's a lot >> so there's a lot Yes, great point.

[00:51:23]There's a lot of social memory tied to um accomplishments in the gym. And not only that, it's it was what he did.

[00:51:33]>> Yeah.

[00:51:33]>> And then you have me on the other end of the spectrum where like I I just don't have that experience at all. Right. And now as a 41-year-old male trying to get into this with low testosterone, low energy, fatigue compounded by all of that, like I struggle with the fact that he wants to get in there every day and he's excited to do it because it's what he has known and has done. And he's he's the one who's helped me identify that, right, too? Because I'm like, "Dude, you're an animal. You want to get in here every day." He goes, "Dude, this is my life. This is what my life has been.

[00:52:07]It's literally been my life's job to do this. And so he's like, it's just different. And so I think for me, uh, when I think about what Debbie said, because I just want to kind of like close the loop on that, like if you're somebody who doesn't experience joy in it, if it's if you're not the Ike in the story and you're more of the Dave in the story, I think the two things you have to cling on to are a the why. Why am I doing it? Because a why can be a big motivator. I also think motivation in general is just overrated sometimes because if we sit around waiting for motivation or even trying to find it, sometimes we never do and we never move.

[00:52:44]But if you're looking for um motivation, one, your why has to be at the forefront. Two, the what like because movement doesn't have to be on a treadmill. Movement doesn't have to be at the gym. None of this stuff. And that's what I want to I'm excited to get into the new space over here and talk about what are some of the things you can do at home without having to go to a gym. And maybe ultimately it does lead you to want to go to a gym and and take it to the next level. But how does somebody have that first take that first step >> um towards movement and the type of movement that's going to increase your your functional uh ability to to move and be h happy and healthy and be you know like great. So, if GLP1s help you uh to not die in your mid60s of a heart attack and instead you're going to live to to your mid 80s, well, how do you thrive in your 80s, right? Because if you if you just get skinny and you improve your your mortality uh by just getting your weight down, but you never work on building those muscles, uh you know, I hear I hear folks a lot say this. I think it's Dr. Tina, who probably says this the most and the most succinctly, so I'll try not to butcher it, but it's like how you move in your 40s will determine how you feel in your 60s. Um, and so just kind of like um just keeping your why at the forefront, but then also understanding that like for me during the summertime, I'm not lifting weights like I was in the winter and the spring, but what I'm doing is I'm outside with my kids constantly. We are getting out and we're moving our bodies. We're fishing. We're swimming. We're we're playing ball in the sideyard. We're we're doing all of these things that our movement like if you look at my um I I don't think Oh, here's my phone. I don't know exactly how to look this up, but like if you look up my Aura ring, which which is my my smart ring that that really tracks just about everything that I do, and you actually look at where I am at in terms of activity.

[00:55:04]Um, how can I pull the like the long-term?

[00:55:12]I don't know if I know how because I'm I'm essentially an old man at this point when it comes to technology, but um you know, every day my my movement is just optimal.

[00:55:26]I mean, there's there's very few days where I'm not right around 100% for for movement. And and that's not working out with a structured thing. That is me just doing things that help me to be a better dad and just like living life, right?

[00:55:44]Um, so I enjoy getting out with my kids and playing ball. I enjoy taking them to the pool. I enjoy these like I enjoy these things. I don't think of them as exercise. So if there's something in your life where you know that you can maybe it's gardening. You get out and you garden. You're squatting. You're doing all these functional movements that you're going to need later in life.

[00:56:05]And so anyways, a high horse. I don't typically give dietary advice and I don't typically give exercise advice, but if there's one thing that I can say that's worked for me, it's find the things that work for you.

[00:56:17]>> Yeah.

[00:56:17]>> Um, and that's like you said, going to be different for everyone. Uh, and it doesn't have to look like going to curves, right? Do y'all remember curves?

[00:56:29]>> Yeah.

[00:56:29]>> I never knew what that was as a kid. I was like, curves? What is it? I thought it was like some I don't know what I thought it was >> club.

[00:56:36]>> I thought it was some lady ladies I thought there where ladies went to school job or something.

[00:56:43]>> Um but then as I got older I realized this oh this is like for ladies working like it doesn't have to be structured is my point. Yeah, absolutely. Absolutely.

[00:56:52]And you know, trying to shift your uh the way that you think about yourself and about exercise.

[00:57:02]Um when you can be more inclusive about what that means, what that looks like, then you can change the narrative, the tape in your head, the label that you've given yourself of I'm not this, I'm not that, I'm not a runner, I'm not somebody who exercises, I don't love exercise.

[00:57:17]And it's not that you have to say the motivational things that I say to myself like, "No, I love exercising." But um but just reframing that you are somebody who's active. You are somebody who likes to move and getting out there. You know, one thing that my family has gotten better at is we like to go for a little walk and season. you know, it's season specific if when we can do it after we eat because we know how much that impacts our health or you know, I'm with my friend and we are both just similar minded and if we eat something then one of us will be like okay let's do some squats for our insulin you know all of that after we eat and we make it fun and we laugh with each other and um we talk about what we can and cannot do anymore and we have we have fun with it but we just you know we do it in the living room we do in whatever outfit we have on. Man, outfits, like having to have the right outfit to work out. I love my husband because both of us are a little neurode divergent and he will just go work out. I mean, he has plenty of outfit specific activities, uh, but he'll just go work out in his outfit, in his clothes, and he doesn't let that become a barrier to him getting it done.

[00:58:31]And that efficiency has helped me a lot because you know getting over that like oh I don't look the part you know no I just moving is a part of my lifestyle.

[00:58:42]Moving is something that's a non-negotiable and so I'm not going to let those things get in the way. I'm just going to do a do a couple squats right here right now.

[00:58:54]>> Yeah.

[00:58:54]>> And that's really been like one of the most effective things to consistency you know. So >> yeah, I've noticed at the camper when u because we spent a few days at the camper this week um this weekend and and even one during the week. Um, and I noticed when, first of all, I noticed whenever I get back, >> I'm like a pound or two lighter >> uh from the camper. And and I think a it's I'm just moving so much more and eating um because there our time is so consumed with activities like we're just always doing something. we're, >> you know, I'm fixing something around the camper or I'm fishing with the kids or we're watching them swim or whatever we're doing.

[00:59:38]>> Walking back and forth from the beach.

[00:59:39]>> Walking back and Yeah. Walking a lot.

[00:59:42]And so you're in this rhythm of of a you're moving around a lot more than you more than I would at home.

[00:59:49]>> Yeah. For some to your bathroom that's like, you know, a good minute or two away.

[00:59:54]>> Yeah. Yeah. So there's just it's walking everywhere. Um, and so, um, I've noticed like that and my blood sugars and regardless of what I eat, which we we eat a lot more whole foods when we're at the camper, too, because we have to be a little bit more intentional. There's not like you don't go out to eat at the camper. You you get meals and you make meals and it's just so much more structured. I'm like, man, if we could if our daily lives could mirror this a little bit more and not, you know, in this like um you know, sort of urban sort of setting where you're driving everywhere and there's convenience everywhere and >> whatever. Um I think we'd probably be better off health-wise. But anyway, uh good conversation. Appreciate it, Ham.

[01:00:36]Appreciate all your uh contributions today and thanks for continuing to be with us even though you're on the road.

[01:00:41]I hope that you get feeling better. Um, having psychosis, >> having psychosporasis on an airplane is probably not on my bucket list for 2026, but good luck with that. Uh, hope that it goes well. Um, and I hope you don't have it. I hope >> Say a prayer for me, everybody.

[01:00:57]>> Hopefully, it's just your body's thrown off from all the travel and get right.

[01:01:02]>> But, uh, thank you all for being here.

[01:01:04]Thank you for being the best part of what we do. If you haven't already, hit the subscribe button, hit the thumbs up button because that trains the algorithm. And then tomorrow, we'll be recording a podcast. I think after this I'm going to run up to the office. They textured the walls and they textured the the ceilings uh at the end of last week.

[01:01:19]So like every day I'm just eager to go see are they painting yet? Are they painting yet? Because it's going to look like a new place when it's painted. And so um I'll post a couple pictures up on the on the YouTube channel here. Uh make sure you follow us elsewhere too though.

[01:01:32]Uh we just hit 30,000 on Instagram where we post a lot of content. So if you're on Instagram >> onthepen.official.

[01:01:39]Uh, but you can find everything at otpinks.com, including all of the sponsors that we talked about today. Um, also ketoshop.com, which provides me with my electrolytes and great tasting electrolytes, by the way. So, yeah, check out otblinks.com.

[01:01:56]Give us a follow somewhere. Check out our sponsors. Thank you for being here.

[01:01:58]Thank you for being the best part of what we do. And we'll catch you on the podcast tomorrow. See you, friends.