The Future of Fitness

[DrJMW]

For the past 10 years or so, biochemists have been exploring the mechanism of lipid synthesis and lipid oxidation and what can be done to solve the obesity problem. Currently, these scientists have discovered that if fat synthesis is blocked--on the cellular level-- then lipid oxidation will dominate (ie fat loss). We know that fat storage is no longer a necessity, for the chances of a famine here are slim to none. So, most of our adipose tissue is unnecessary (that's where the 6%BF and 10-12%BF kick in). So, by blocking fat storage, the body is forced to use up its remaining fat for repair and energy. Previous attempts included HCA (hydroxycitric acid), which attempted to block fat synthesis early in the cycle, but not at the rate-limiting step (this is where the cycle needs to be blocked). A cancer drug, c-78, was found to block fat synthesis at the step after the rate-limiting step. The problem here was it also blocked appetite, so the subjects never ate enough food for repair and energy.

The good news. Scientists at Baylor are working on a med that will block the rate-limiting step, thereby inhibiting fat synthesis and allowing for appetite. They believe that this med will be out in 3-5 years. In addition, they have located the gene that causes inhibition of the fat storage process; once genetic manipulation becomes the rule, then people can be made "fat free" on the genetic level at birth. If this comes out, it will change everything.

 

[Sassy69]

Its nice to have the technology..... but can you say "genetic engineering"...? This is probably going to be a great field for future lawyers! Imagine the people who sue because they might have wanted to be fat but had that choice taken away from them as children. I recall a "Twilight Zone" episode where you could choose to become one of a set of models who were "perfect" - so everyone looked the same. Except this one girl who was sort of geeky looking, alittle overweight with glasses, who just wanted to be herself.

Anyway, just playing the devil's advocate here... interesting stuff tho. So where do I sign up for some of the "test groups" for this med??

 

[Imnotdutch]

I hate to burst your bubble but......

Locating a gene and being able to manipulate it to get a desired result are two things that are decades apart......thats if it can be done. It is becoming obvious that very few traits are controlled by a single gene.....particularly important ones such as control of bodyfat. It is more likely that they have found 1 gene of several involved in fat storage inhibition.....not all of them. Until the role of every gene from the human genome has been assigned, which is many many years away, nobody will know whether that gene alone is the key. If it isn't, then manipulating it may have little or no effect. Many genes are being identified that have commercial potential....but very few actually turn out to be as useful as predicted.

But lets assume that you know the only gene involved.....you now have the problem of either inactivating the gene through DNA manipulation, which cant be done with any great level of success yet, and if it could there is alot of opposition to this approach (as Sassy pointed out).....or you have to inhibit the gene product. In order to inhibit the gene product you have to have a good understanding of the protein you are dealing with. Again that takes many years to do. Assuming you do find the inhibitor.....you have many years of trials ahead of you to make sure that it is specific. Usually these things have a habit of looking good for a long time, particularly when looking at the gene product in isolation or at cell cultures (even in model animals sometimes), then you find out about all of the bad things that happen when you manipulate it in a real live organism.

BTW the guys at Baylor predicting results in 3-5 years prob dont know how long it will take. Scientists have a habit of being very optimistic about their work in public......thats how they get money to fund their research (quite sad really). So I wouldn't read too much into their numbers. There are many people, in many labs, working on these potentially useful projects......but its the nature of the beast that very few reach fruition.....and if they do, it takes many years. So dont hold your breath.....

The good news. Scientists at Baylor are working on a med that will block the rate-limiting step, thereby inhibiting fat synthesis and allowing for appetite. They believe that this med will be out in 3-5 years. In addition, they have located the gene that causes inhibition of the fat storage process; once genetic manipulation becomes the rule, then people can be made "fat free" on the genetic level at birth. If this comes out, it will change everything.

 

[Imnotdutch]

BTW, why does the cycle have to be blocked at the rate limiting step?? Is this something specific to this cycle?? because I cant for the life of me think why it would be a general requirement.

 

[MS]

Good comment imnotdutch. You and I seem to be or interested or working in similar fields and maybe we should carry on some discussion off of these boards????

Aside from the ethical issues that will prolly never be resolved (it's a bit like religious issues) there is are too many practical issues to even begin to speculate publically. Animal models of obesity, hunger, satiety and mass gain (addiction, alcohoism etc....)are still a world apart from the human condition. Obesity problems are almost certainly more like psychiatric problems in that they are highly multigenic.

We're all holding our breath for that magic bullet but the realist knows that it doesn't exist, and if it did, the powers that be would restrict it's distribution to the wealthiest humans.

 

[DrJMW]

The scientists at Baylor have already isolated and modified the gene in rats. The modified rats are healthy in every aspect...and they eat like pigs and do not gain any fat. Basically, the gene inhibits acetyl Co-A carboxylase. This enzyme (the rate-limiting step) is responsible for the conversion of Acetyl Co-A to the first, primary fatty acid. Genetic manipulation, in humans, is not the immediate goal of the group. They believe that they can create a medication that will inhibit acetyl Co-A carboxylase. There are two groups of chemicals now that are used as weed killers, and this is exactly what those chemicals do.....just wanted everyone to be aware of this research. I find it exciting.

 

[Imnotdutch]

MS: I work as a protein chemist but have a pretty broad interest. I always find it interesting that people get all excited when a gene has been identified as potentially useful and believe that we will be able to manipulate it in 3-5 years.


Dr: If all they have is a mouse model you are looking at alot of work. Inhibition studies are never easy.....lots of false leads. Believing something can be done and actually doing it are two different things. Every scientist believes the work he proposed, and in turn got money for, can be done.

The scientists at Baylor have already isolated and modified the gene in rats. The modified rats are healthy in every aspect...and they eat like pigs and do not gain any fat. Basically, the gene inhibits acetyl Co-A carboxylase. This enzyme (the rate-limiting step) is responsible for the conversion of Acetyl Co-A to the first, primary fatty acid. Genetic manipulation, in humans, is not the immediate goal of the group. They believe that they can create a medication that will inhibit acetyl Co-A carboxylase. There are two groups of chemicals now that are used as weed killers, and this is exactly what those chemicals do.....just wanted everyone to be aware of this research. I find it exciting.

 

[DrJMW]

I still find the research interesting--the biochemist leading the research team (Kalil...can't remember his name) has been working on this for over 25 years. If he does it, looks like a Nobel to me. I'm rooting for him.

 

[SteelPreacher]

O.K.- I'm not a doc or a Chem and I very much respect what y'all have said up to this point but lets say for a moment that this is all true; Either you take the pill or you are genetically engineered as such. Why will anyone have to go to our beloved gym anymore? There's really no need for hard work when you can just manipulate as you please. Where's the fun in that. There won't be such thing as fat people or ugly people we will all be planned out before hand Yuck! What happens if something goes wrong in the process do we throw them out and start over or what. You say Exciting I say Very Scary!

 

[Imnotdutch]

A nobel prize for producing yet another drug using tried and tested techniques?? I cant see that happening myself.....but you're entitled to your opinion.

Presumably you mean a nobel prize for Medicine/Physiology?? Take a look at the last 5 years winners:

1996: The specificity of cell-mediated immune defence
1997: Discovery of prions
1998: Nitric Oxide as a signalling molecule in the CV system
1999: Intrinsic targetting signals in proteins
2000: Signal transduction in the nervous system

What do all of these things have in common? The reason they are important is because they have far reaching repercussions. They affect many people and explain many previously unexplained observations. In the work that you describe they are using known techniques to inhibit yet another cycle. Big deal! Its good work......but it isn't in the same class as the work mentioned above.

I still find the research interesting--the biochemist leading the research team (Kalil...can't remember his name) has been working on this for over 25 years. If he does it, looks like a Nobel to me. I'm rooting for him.