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Sep. 10th, 2004 11:57 pm![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
zdashamberSo, I mentioned in a comment over at ![[livejournal.com profile]](https://www.dreamwidth.org/img/external/lj-userinfo.gif)
arden_ranger's place that I sat in on a neat seminar Wednesday about the genetics behind obesity. Here's a bit more with the explaining:
The guy talking was Michael Leitges. He spoke of a (the?) basic system underlying energy-storage-regulation. He was saying that, for example, a tall guy who works in a field and might need to take in 2500 calories a day, if his energy balance was off by even 1% (to be taking in 2525 calories a day), he'd be gaining 2 pounds a year. And yet, he said, people don't expect to gain two pounds a year, it's not the norm—so the body's energy regulation should when it's working have a better than 1% accuracy. That, I didn't buy; he had at the same time charts that showed how people tended to be fit in their 20s and then overweight by their 40s. What, does that all suddenly happen at 35? But anyway, most of the talk was about the wild mutant cases that lead to far more than 40 lbs per 20 years...
So, the basic building block of the energy-regulation system, as I gathered, is leptin. Leptin is a hormone made by fat cells, which floats through the blood to the brain, where its levels are constantly checked.
The first big break they had in the genetics-of-obesity field was finding a mouse in which the gene that made the leptin-producing protein was mutated so that the protein didn't work, and no leptin was being produced. At which point the brain is like, "Oh my god, I'm not getting a fat signal I have no fat reserves I'M STARVING TO DEATH EAT EAT EAT EAT"... You understand, I'm providing my own dramatizations, here. Anyway, there was a great photo of a normal mouse next to a mutant mouse so fat it was the size of a guinea pig.
So, they found that the same gene knockout in humans lead to the same sort of phenotype. But it's rare... I forget, I think about 2% of all obese people have that particular trouble.
But what about the receptor in the brain that catches the leptin as it floats past? What happens when that's knocked out? Same thing. (Brain: "AAAAAAA! I'm not getting a leptin signal! I have no fat reserves!") Another 2% of obese people accounted for.
But noooo, nothing is that simple. That receptor triggers another two proteins, and they have to be caught by yet more receptors, and then those receptors trigger other proteins, and on and on and on... I swear to god there are so many damn interacting proteins in every cell, all the time, it's a wonder that anybody survives. Thousands of 'em. At least. You hear we're 98% like chimps? That's because most of the genes we have are absolutely necessary for survival, just like they are, any change whatsoever fatal...
So, Letiges was talking about how he looked at one of those secondary receptors and found that yes, people with mutations in that became obese. Not as obese as the ones without leptin, though, interestingly, suggesting that there's another path for the signal to get to the "stop eating" centers. And he's guessing he's got another 3.5% of obese people covered.
So how's this all help? Well, the sans-leptin people, there was a sorta heartwarming story; there was a picture of a toddler who already looked like a sumo wrestler, and then they figured out he lacked leptin and started giving him injections of it. Next picture, at 9, he looked like a normal kid again. Awwww.
For the receptor people, things are trickier. Is there, perhaps, some drug that will make a just-barely-crippling-along receptor into a nearly-working-fine receptor? Could be. Is is possible to inject the next-step-along protein directly, so the missing receptor is leapfrogged? Possibly. These are things that drug companies will be all over...
Can the body be tricked? I'm guessing wildly that stomach-stapling works because the brain is freaking out with the EAT EAT EAT and the stomach says, "Hey, all full, good buddy" and the brain says, "My work here is done." And then there's a latency time for the brain to get worked up again. So, how does the stomach signal that it's topped off? Can that be duplicated from the outside with drugs? Probably...
Then there's the aspect that brought this guy to my workplace. We're doing addiction stuff. Can the desire for food be dialed down? (Brain, sucking on cigarette, with French accent: "I would be worried that I was starving, but somehow, it all seems so pointless...")
And then there's the question, Is there a good way to lower the activation energy to get people off of their arse and into a gym?
And what about the diversion of energy into storage? Surely it's possible to excrete it, instead.
And I'm sure there are other aspects that haven't bounced across my mind. I reckon, though, that there are plenty of scientists working on each of these things... In addition to the cure for obesity being a huge cash cow, the WHO has declared it right up among the top diseases endangering the rich parts of the world. (And actually, looking for a specific rank, I found a neat article about genetics and obesity in the Atlanta Journal Constitution...)
And I reckon that in the next few decades, we will learn almost every step in every relevant pathway, and be on our way to having good sticks to poke each protein with.
I'm really, really looking forward to it. In closing, I'd like to say, [high school football voice] Genetics Rock! [/voice] Thank yew.
arden_ranger's place that I sat in on a neat seminar Wednesday about the genetics behind obesity. Here's a bit more with the explaining:The guy talking was Michael Leitges. He spoke of a (the?) basic system underlying energy-storage-regulation. He was saying that, for example, a tall guy who works in a field and might need to take in 2500 calories a day, if his energy balance was off by even 1% (to be taking in 2525 calories a day), he'd be gaining 2 pounds a year. And yet, he said, people don't expect to gain two pounds a year, it's not the norm—so the body's energy regulation should when it's working have a better than 1% accuracy. That, I didn't buy; he had at the same time charts that showed how people tended to be fit in their 20s and then overweight by their 40s. What, does that all suddenly happen at 35? But anyway, most of the talk was about the wild mutant cases that lead to far more than 40 lbs per 20 years...
So, the basic building block of the energy-regulation system, as I gathered, is leptin. Leptin is a hormone made by fat cells, which floats through the blood to the brain, where its levels are constantly checked.
The first big break they had in the genetics-of-obesity field was finding a mouse in which the gene that made the leptin-producing protein was mutated so that the protein didn't work, and no leptin was being produced. At which point the brain is like, "Oh my god, I'm not getting a fat signal I have no fat reserves I'M STARVING TO DEATH EAT EAT EAT EAT"... You understand, I'm providing my own dramatizations, here. Anyway, there was a great photo of a normal mouse next to a mutant mouse so fat it was the size of a guinea pig.
So, they found that the same gene knockout in humans lead to the same sort of phenotype. But it's rare... I forget, I think about 2% of all obese people have that particular trouble.
But what about the receptor in the brain that catches the leptin as it floats past? What happens when that's knocked out? Same thing. (Brain: "AAAAAAA! I'm not getting a leptin signal! I have no fat reserves!") Another 2% of obese people accounted for.
But noooo, nothing is that simple. That receptor triggers another two proteins, and they have to be caught by yet more receptors, and then those receptors trigger other proteins, and on and on and on... I swear to god there are so many damn interacting proteins in every cell, all the time, it's a wonder that anybody survives. Thousands of 'em. At least. You hear we're 98% like chimps? That's because most of the genes we have are absolutely necessary for survival, just like they are, any change whatsoever fatal...
So, Letiges was talking about how he looked at one of those secondary receptors and found that yes, people with mutations in that became obese. Not as obese as the ones without leptin, though, interestingly, suggesting that there's another path for the signal to get to the "stop eating" centers. And he's guessing he's got another 3.5% of obese people covered.
So how's this all help? Well, the sans-leptin people, there was a sorta heartwarming story; there was a picture of a toddler who already looked like a sumo wrestler, and then they figured out he lacked leptin and started giving him injections of it. Next picture, at 9, he looked like a normal kid again. Awwww.
For the receptor people, things are trickier. Is there, perhaps, some drug that will make a just-barely-crippling-along receptor into a nearly-working-fine receptor? Could be. Is is possible to inject the next-step-along protein directly, so the missing receptor is leapfrogged? Possibly. These are things that drug companies will be all over...
Can the body be tricked? I'm guessing wildly that stomach-stapling works because the brain is freaking out with the EAT EAT EAT and the stomach says, "Hey, all full, good buddy" and the brain says, "My work here is done." And then there's a latency time for the brain to get worked up again. So, how does the stomach signal that it's topped off? Can that be duplicated from the outside with drugs? Probably...
Then there's the aspect that brought this guy to my workplace. We're doing addiction stuff. Can the desire for food be dialed down? (Brain, sucking on cigarette, with French accent: "I would be worried that I was starving, but somehow, it all seems so pointless...")
And then there's the question, Is there a good way to lower the activation energy to get people off of their arse and into a gym?
And what about the diversion of energy into storage? Surely it's possible to excrete it, instead.
And I'm sure there are other aspects that haven't bounced across my mind. I reckon, though, that there are plenty of scientists working on each of these things... In addition to the cure for obesity being a huge cash cow, the WHO has declared it right up among the top diseases endangering the rich parts of the world. (And actually, looking for a specific rank, I found a neat article about genetics and obesity in the Atlanta Journal Constitution...)
And I reckon that in the next few decades, we will learn almost every step in every relevant pathway, and be on our way to having good sticks to poke each protein with.
I'm really, really looking forward to it. In closing, I'd like to say, [high school football voice] Genetics Rock! [/voice] Thank yew.