4 Burst results for "Jules Hirsh"

"jules hirsh" Discussed on The Peter Attia Drive

The Peter Attia Drive

05:22 min | 2 years ago

"jules hirsh" Discussed on The Peter Attia Drive

"Diet, those substrates themselves metabolites, you mentioning fatty acid, but many other things change may themselves have effect on the drive to eat on sympathetic to that idea and exactly in any given individual who does or doesn't respond to a specific diet, which of the mechanisms, you know, whether it's a current the level of the taste of the diet or some of the metabolic consequences of the diet. I would say. Say to the extent that somebody is successful in losing weight on that diet. A they have to be negative energy balance that there's no way that they can eat the number of calories that they're expending and lose weight. So they need to be a negative energy balance. And I mean, that's just a given and then the mechanism by which the diet composition influences. The success of their ability to sustain a Hypo caloric state, which as you pointed out is uncomfortable from open to the possibility that it could be at any level of the sort of neural circuitry that regulates food intake could be very proximal terms of taste aspects. But it could also be some of the mechanisms that you that you mentioned I think that's perfectly perfectly reasonable how that works as you pointed out is a tough nut to to figure out. And I think like you said. There are individuals who respond very well to diet of quite divergent composition, but they have to be taking less calories than they are spending. Right. And that's an easy thing to do mathematically. It's a very hard thing to do clinically. Because again, I think patients can tolerate a lot. But I don't think people can tolerate hunger for very long. I think to ask somebody to be constantly hungry is a losing proposition. And that's why I believe clinically low carbohydrate diets seemed to be more satiated, and again, whether they're satiated because of something in their composition or whether they're just say sheeting because you end up eating more of yourself. I mean, I've seen lots of patients who an and this is even been published who on sixteen seventeen hundred calories a day of Kita genyk diet seemed completely fine and yet Ansel keys patients at fourteen hundred fifteen hundred sixteen hundred calories of basically, very hard high carbohydrate diet, very low fat. Diets lost their minds. What did you believe ten years ago that you don't believe today to be true? I think over the past decade the field of the sort of neuroscience of body, weight regulation or ingested behavior and energy expenditure has expanded the. Role of other elements in the central nervous system beyond. What began as are very intense focus on the hypothalamus, partly that's historical, and for reasons having to do with the trackability of some of the cell types and mechanisms in the hypothalamus, but say the biggest change in my thinking about this has been that these Supra hypoth- Alantic aspects of the central nervous system again starting with the cortex and working down have a much stronger. I think ultimately impact on this regulatory system than the way I perceived it a decade ago. And what does does is it opens up? I think a lot of very interesting aspects of the biology that may be we weren't either capable over didn't focus on adequately part of which actually is in response to the point. You just raising that is what is the effective dia composition on hunger. And so forth. It's almost certainly an aspect of this sort of view of the broader central nervous system impact on ingested behavior than just the hypothalamus. You, you know, my mentor Jules Hirsh think who fortunately way for years. Yeah. The three years ago he would agree with this. I mean, he always I think was suspicious of focusing. You know, slavishly if you will on the hypothalamus as the center for all of this. He always I think at a much broader perspective on some of the psycho affective aspects as he would describe of congestive behavior. And I think he would see the sort of flowering of broader view of some of these regulatory aspects of food intake to other parts of the central nervous system. He would say I told you so and he was right hide things looking down at you say, he's probably say. By this stuff. If we get away of magic wand and not only were resources unlimited, but more importantly, any of the technical considerations. That make this type of study challenging were just ameliorated. What's the dream experiment? You would wanna do if you got one more shot at this. You could spend the rest of your career doing a dream experiment with infinite resources, infinite Subject Participation screw the ethics..

Jules Hirsh Ansel fourteen hundred fifteen hundr sixteen seventeen hundred calo three years ten years
"jules hirsh" Discussed on The Peter Attia Drive

The Peter Attia Drive

05:08 min | 2 years ago

"jules hirsh" Discussed on The Peter Attia Drive

"Consequences of deleting this region of the chromosome fifteen by mechanisms that are somewhat complicated influence, the expression of a enzyme called pro convert as one and this enzyme is critical for the processing of many of the hormones in neuro peptides that are made in the body. They virtually all hormones in Europe tides are made as pro hormones that his precursor hormones that are then processed by pro converters one. And that is what produces or generates the mature form of hormone or neuro peptide, and we think actually that the FINA type many of the FINA types of the Prater willy patients may in fact, be due to a deficiency under activity of pro converted one which is not in the interval where this delete. Occurs, but is influenced downstream by one or another of the genes in that in that interval, and it's relevant in the question of insulin. Because insulin is processed by pro converted. So some of the answer this peptide gets cleaved pre hormone, correct? So some of the hyperinsulinemia of the Prater willy might be pro insulin insulin pro insulin has biological activity but much lower than native insulin. And so if this turns out to be the case, then it might be possible to rectify some of the prouder Willie phenotype by being able to increase the activity of one pharmacologically or by other means, so there's all this incredible work. All this incredible molecular biology, molecular genetics, that's identified leptin deficiency left a receptor deficiencies. The cluster of defects, depressed or Willie. And yet the question is how much do these things tell us about the more broad condition of obesity that afflicts I don't even know the stats. I don't really keep track of this stuff anymore. But I don't know what a third of Americans are probably now. So I'll tell you an interesting perspective on that question in I mentioned earlier while it we were doing the efforts to clone. These genes I was studying patients in clinical research center, Jules Hirsh, Mike, Rosenbaum, longstanding associates what we were doing is looking at the metabolic consequences of weight reduction and showing that if you reduce the body weight of human by ten percent twenty percent, you get a reduction in energy expenditure, which is greater than what you would predict from the loss of just body size or that they're in other words their metabolic rate didn't reduce just to support the new reduced weight. Reduced even further which would almost try to return them to have your weight. Right. So they had a disproportionate reduction in energy expenditure. And some of the data suggested that the major change in energy expenditure was not in resting metabolic rate. But in the energy cost of low levels of physical activity of muscle work, so to speak, but at very low levels of activity, and we went on to show that as you would expect based on a lot of what we've been talking about the leptin levels were low in these individuals low but proportional to the reduced amount of body fat. So one hypothesis that we had is that this reduction in energy expenditure was in fact, a reflection of the fact that the body was sensing the reduction and low in leptin and interpreting that as a starvation state that is for that individual that new lower body. Wait represented a threat if you will to survival or reproduction and we've done experiments subsequently in which we've injected leptin into those individuals. None of them has genetic Asian of so they're just wait reduced normal individuals. We've put leptin back into them by injection to raise the blood level back to where it was before they lost their body weights. These very low doses of Lebanon, and that intervention will restore their energy expenditure back to where it was before. They lost the body weight. Even though they're now still maintaining the lower body way. So put this in some quantitative terms for me that infusion of leptin gave them how many more cake helper day in energy expenditure. All things equal between movement activity at cetera talking about one hundred cake Halliday like what kind of adult are produced two or three hundred because. These are big start with a met. That's a huge delta. Right. And we could show that that affect is primarily being conveyed through skeletal muscle..

Prater willy FINA Europe hyperinsulinemia Willie Halliday Jules Hirsh Lebanon Rosenbaum Mike twenty percent ten percent
"jules hirsh" Discussed on The Peter Attia Drive

The Peter Attia Drive

04:16 min | 2 years ago

"jules hirsh" Discussed on The Peter Attia Drive

"And this was around the time that it was becoming clear that hormones head receptors that were specific to those hormones like thyroid, insulin growth hormone, so Coleman hypothesize that the OB. Mouse was missing what we refer to as the ligon, the circulating hormone and db mouse was missing the receptor for and it turns out that Dr Coleman was right everything. You've just said was known by what point in time. I would say by the late nineteen seventies. Okay. So just as your coming on the scene, the whippersnapper who doesn't know shit. Yes. The guy up Jackson up in Maine knows this. And you can't wait to get all over this. Correct. So I began. By actually studying adipose tissue to see whether there was something that might be regulated by adipose tissue that would fit in this sort of general category of something that might produce a signal or might be related to the to the anatomy of the adipose tissue time. Jules Hirsh was particularly interested in the fact that it appeared that what happens when people get obese is that they're fat cells expand up to sort of maximum size, and then new fat cells begin to appear whether they were mayday Novo or had been resting in the area of the other Oedipus. I wasn't clear at the time. But what happens as people get more and more obese that more and more fat cells are recruited so that if you look at a very obese individual, they have what is referred to in the literature is hyper plastic at oppose tissue. They have more fat cells jewels it actually figured out. At a way to count the fat cells of a human being, and you can look under a microscope and see how big the fat cells are. So he was very interested in what it is that permits of big fat cell to call up. If you will the other fat cells that are going to be needed. Once it reaches a critical size, and whether these fat cells were generating something that might act like signal are there any organs inside a fat cell. Oh, yeah. Fats has the complete repertoire organize that any other cell. Does got it's got a regular, quote, unquote, regular nucleus. It's got might a Condra. Yeah. Yeah. Yeah. It's got the whole. It's just it's site. A plaza is dominated by these lipid droplets, it's designed to be able to hold these use lipid droplets. But otherwise is a perfectly respectable cell has all the all the other components and what jewels had been doing along with another investigator in the lab or foul. Oust was extra painting at oppose tissue from rats. They were working primarily with rats. Although there was some OB mice around. I'd actually seen those when I was at Harvard in Boston into chronologies train me talk to me about him. But jewels in Irv were extirpated at oppose tissue depots from rats and looking to see what happened in one of the things that they were struck by is that when they took a fat pad out if they waited long enough and just let the animal eat whatever wanted to eat. It would eat its way back up to restoring that fat pet through the Novo creation of more fat cells. You leave the capsule of the depot there, and is able to regenerate new fat cells and they fill up, and they don't fill up to three times the size that they were before they go right back to the appropriate size for that depot. And. One of the things that jewels and Irv for very interested in how does the animal what has animal know that it should eat a little bit more to be able to generate the fat. That's been extirpated into this experiment. Only work when you started with obese rats or did it work if you took a lean rat as well it work with lean rats just as well. As a matter of fact, most of the work they did was with lean rats or not not genetically obese now speaking of rats..

Dr Coleman Irv growth hormone Jules Hirsh Jackson investigator Maine Harvard Condra Boston
"jules hirsh" Discussed on The Peter Attia Drive

The Peter Attia Drive

04:57 min | 2 years ago

"jules hirsh" Discussed on The Peter Attia Drive

"I came to New York actually after looking around in the Boston area for someone who could mentor me in this kind of activity, and it turned out there. I mean, there's some interesting stories about that. But the advice that I got from the people who are not in a position to help me in the way that I thought I needed help was that I might consider going to the Rockefeller and working with the physician scientist named Jules Hirsh who would time was very interested in the biology of adipose tissue from a number of perspectives, and I had actually communicated with Dr Hirsch in the literature by commenting on some of the work that he had done with regard to add up sites and signals that might come from adipose sites that affect potentially food intake and body weight. This was an area that he was quite interested in and I. I was to based on some of the thinking I had done about it while I was in the training in Boston. And he, and I actually had a communication in the literature on some of the work that he had done, and I went actually to visit his laboratory, and while I was in New York for an entirely different reason. And it was very shortly. After that that I move which is another great example of the types of common threads, we see in great scientists whether they be scientists or physicians I and his which has mentorship right again. Every person I talked to who's done something remarkable in science can point to mentors a mentor or mentors. And obviously for you Jules was probably the most important mentor. I'm guessing that's right. I had very important other mentors in the area of clinical medicine and the one who trained me and indoor chronology individual again of physician, scientists more clinically oriented name. Jack Crawford himself was. Very interested in the role of body fat and its interaction with other physiological systems in the body, most notably onset of puberty, and it was he actually put me in contact with another scientists at Harvard name rose Frisch who also was very interested in why for example, young women who lost weight as a result of anerexia or more commonly in her experience dude of very vigorous physical training for things like distance running or bicycling swimming became a Minarik. In other words, there period stopped and rose was very curious about why this was and whether there was a communication between fat and parts of the brain regulate the Kanada axis, which is the hypothalamus again. And I remember having many conversations with rose about where the signal might becoming from. She thought it actually might be coming from. Adipose tissue at sites in the bone marrow. And it was always encouraging me to study bone marrow. As a source of whatever this signal might be. So what year did you arrive at Rockefeller, nineteen seventy eight at that point in time was the adipose tissue was at a post cell where they it was this regarded as an inert sort of storage depot for fatty acid, or was it considered an endocrine organ, like what was the state of thinking about fat at that time the view of the role of adipose tissue was very strongly in the direction of the sort of former characterization that you made which is that it was a passive depot for fat. In the form of storing free fatty acids as triglycerides, so that they were hydrophobic. So that you could pack a lot of calories into organ or into cell without having a lot of water there. So it's very efficient way of storing energy, actually, as you know to probably around nine calories per gram. And its role as a signaling device or an integration. Organ was really people were thinking about it. But there was no firm evidence in this regard, other than I think the increasing sense that the size of the adipose mass was doing something to the levels of circulating insulin that somehow insulin rises when the fat mass rises the mechanism or the release of the other way around was clear where which direction so at the time, I think the view was pretty much as fat mass increases the concentration of insulin rises to to meet the consequences of so-called, insulin resistance, which occurred not only in adipose tissue. But maybe more importantly in liver and muscle..

Minarik Jules Hirsh Boston Jack Crawford New York Dr Hirsch Organ scientist rose Frisch Rockefeller Harvard nine calories