A new target for modern day ills??

[MS]

The role of melanin-concentrating hormone (MCH) in feeding behaviour has been well established in recent years, leading to interest in the possibility of antagonizing its action as a therapeutic approach to obesity. Now, as Borowsky et al. report in Nature Medicine, antagonists of one of the two receptors that mediate the effects of MCH might have promise not only in the management of obesity, but also as a treatment for depression and anxiety.

Screening for compounds that bound to MCH receptors led to the identification of SNAP-7941, an inhibitor of the MCH-1 receptor that has 1,000-fold selectivity over the other receptor for MCH, and also over other receptors associated with food intake, such as the receptor for neuropeptide Y. Pre-treatment with SNAP-7941 inhibited the increase in food intake elicited by MCH, supporting a role for this receptor in mediating MCH-stimulated food intake.

But would pharmacological blockade of this receptor reduce body weight, or would compensatory mechanisms come into play? The authors found that acute treatment with SNAP-7941 decreased palatable food intake in rats, and that chronic treatment resulted in a marked, sustained decrease in body weight in rats with diet-induced obesity, providing strong support that this receptor is a viable target for the treatment of obesity.

Although MCH has been studied most extensively in relation to food intake and body weight, the distribution of SNAP-7941-binding sites and receptor immunoreactivity in specific regions of the brain, indicated that MCH might be involved in mood regulation and anxiety. To investigate this, Borowsky et al. evaluated SNAP-7941 in three animal models of depression and/or anxiety, and compared the results with those for clinically approved drugs. In one of the tests, which is an experimental model of depression, the profile of SNAP-7941 was similar to the selective serotonin-reuptake inhibitor fluoxetine (Prozac), and in the rat social-interaction test, which is a model of anxiety, the profile of SNAP-7941 was indicative of an anxiolytic (calming) activity similar to the benzodiazepines (such as Valium). Finally, in the guinea-pig maternal-separation vocalization test, which is a model of anxiety and depression, the responses to SNAP-7941 were comparable to those to buspirone (Wellbutrin). So, although the role of MCH in human psychiatric disorders remains largely unknown, it seems that further assessment of MCH receptor antagonists for the treatment of depression and/or anxiety could be warranted.

So the question is, where can we get our hands on some to try it out!!??!!

 

[SteelWeaver]

You could try siphoning some out of your brain ...

How interesting that they use animal models of anxiety/depression to extrapolate from - is there a chemical parallel, despite the hugely different psychology? Can animals be said to have a "psychology"? Are these models really comparable enough to humans for conclusive results?

I wonder if an adequate and workable nutritional model could be built and then taught from day one in schools, and sugar and saturated fats regulated as scheduled drugs, if we couldn't somehow more cheaply and easily solve the obesity epidemic?

 

[MS]

You think " an adequate and workable nutritional model could be built and then taught from day one in schools, and sugar and saturated fats regulated as scheduled drugs" would be a cheap and easy option?????!!!!!

As for syphoning off of brains, I don't belive SNAP-7941 is necessarily a naturally occuring brain chemical. It's just a compound that happened to bind to the receptor they were interested in. They prolly threw thousand and thousands of compounds at these receptors. Ummmmm, just like Prozac is doesn't naturally occur in our brains.

Rats are not like humans in many ways, but some of the rat 'models' of human depression and anxiety are strikingly similar in their behaviour and response to the same stimuli that differentiates healthy humans from humans with specific psychiatric disorders. Admittedly they can't communicate directly that they feel hopeless, agitated etc..., but there are ways that normal and healthy (happy?) rats/humans respond to stressors, and then there are the responses that unhealthy/unhappy rats/humans will display.

Of course, until it's been tried in humans, it's all just intriguing.......after all, clenbuterol shreds fat and increase LBM dramatically in most mammals, and leptin reduces feed intake in obese rats, and many other drugs that work in rats have not had the same effect in humans. Again, this no doubt has a lot to do with eating as a social and emotional crutch in humans, and all of the attendant advertising and other pressures to eat when we're really not hungry.

 

[SteelWeaver]

I did say *if*. Perhaps not "easier", but almost certainly cheaper. I mean, if we take all the billions that are spent on research and marketing of drugs for obesity, the billions that are spent on crap sugary foods, and the billions that are spent trying to mop up the health disasters that over-consumption of those foods leave in their wake, we could surely find some spare cash for a more balanced food rectangle or pentagon, or square, or whatever, and then habitualise everyone to eating healthily before they're old enough to rebel.

Habitualisation is a powerful tool.

 

[MS]

"Habitualisation is a powerful tool."

Pizza, chocolate and TV are equally powerful

 

[SteelWeaver]

Ya think? I dunno. I think a lot depends on what you're used to. But then, I may be entirely wrong. I was going to say, for example - I was raised on comparatively little junk food, little TV, a lot of books and a healthy dose of pretty serious exercise every day. As an adult, I find TV mind-numbingly boring, exercise and books a huge thrill, and mostly didn't eat any junk until this whole diet-down-to-crazy-levels-of-bf started.

On the other hand, my older brother and sister, raised in the same environment, are now both obese or close to it, watch TV daily, and eat a lot of crap.

Sigh.

A huge team effort on the part of educated and intelligent humans WILL solve this problem someday. And maybe they can cleverly solve the problem of MALnutrition while they're about it. I intend to be a part of this effort.

... first.... I'll need some rats ... mwaa haa haa

 

[circusgirl]

Ya think? I dunno. I think a lot depends on what you're used to. But then, I may be entirely wrong. I was going to say, for example - I was raised on comparatively little junk food, little TV, a lot of books and a healthy dose of pretty serious exercise every day. As an adult, I find TV mind-numbingly boring, exercise and books a huge thrill, and mostly didn't eat any junk until this whole diet-down-to-crazy-levels-of-bf started.

On the other hand, my older brother and sister, raised in the same environment, are now both obese or close to it, watch TV daily, and eat a lot of crap.

My 'rents fed me healthy food. I got to eat sweets (candy and chocolate) on Saturday. I have EXCELLENT teeth, although both mum and dad have bad teeth themselves. TV was rationed to 1 hour excluding news coverage a day, and any special sporting occasions. We got 2 hours at the weekends. Betime right up to when I was 16 was 10pm, very few exceptions (so they could have time to themselves, I guess).

For many years afterwards when living on my own I was lazy, no exercise, pigged out on junk, etc. BUT I still LIKE salads, yoghurt, beans, lentils, chicken, veggies... And now that I'm a healthier person, I LIKE the healthy food (well, most of it). Beansprouts are a fav in fact, as are brown lentils. (I also like pizza and chocolate, but so does everyone). We have no TV as I had a housemate who had to have the damn thing on all day for about a year and swore I would never miss tv again. I love reading. Exercise is fun.

I guess people either react strongly against healthy upbringing or stick with it.

I hate to see overweight little kids though, as they are less likely to lose the fat in adulthood, more likely to develop compulsive eating disorders due to being picked on for being fat, more likely to get diabetes/heart disease etc, less likely to be active as the active kids pick on them.....

BTW cats and dogs do develop clinical depression and also self-mutiliating disorders in certain circumstances, and there is pet prozac. Since depression is a biochemical ailment, no reason the CNS of dogs and cats can't get diseased. People can intellectualise it though, dogs just look depressed...

circusgirl

 

[MS]

"A huge team effort on the part of educated and intelligent humans WILL solve this problem someday." Ya think????

I am more pessimistic. The biggest problem is that there really are very few educated and intelligent humans around, and solving the problem would require EVERYONE to become educated and intelligent in matters of nutrition and exercise, not to mention highly motivated. Now if my nutrition professors couldn't manage to stay trim and fit, what chance is there for lesser educated and less motivated people in a world full of choices?? Not good.

If you lived in a dictatorship where you could attempt to control the food and exercise of the people under your control, you might have some success. After all, this is basically how obese lab mice are coerced into losing blubber......the lab researchers have complete control over their food intake. But as soon as you allow those mice access to unrestricted food, they will become obese. And in this hypothetical dictaorship you would also create a huge blackmarket for 'illegal' foods.

"I guess people either react strongly against healthy upbringing or stick with it."

Well said circusgirl!

Now about this SNAP-7941.....I don't seriously think it will be a cure-all for modern problems. It's just and interesting compound that may have some clinical applications. Sure, it may curb apptite and reduce bodyfat, depression and anxiety, but what affect will it have a someone's ability to gain and retain LBM??? My suspiscion is that anything that acts in a manner similar to benzos, Prozac, and appetitie suppresants is NOT going to be optimal for bodybuilders wishing to gain some serious muscle. But only time will tell......

 

[JJFigure]

I grew up in a family of 9 children; we all tend to eat too fast because that was the only way we would get enough food at the table. That's a habit I'm still trying to break, and I haven't lived at home in 10 years.

We didn't get a lot of junk food growing up, mainly because Mom and Dad didn't have the money; we grew up on a farm, grew our own vegies, had livestock, etc. So potato chips and candy were treats. For some reason, this had the opposite effect on me - put some candy in front of me and I'll eat ALL of it. I may get sick, but I'm eating the whole works.

As far as tv - we didn't watch much of it growing up, and I still don't. I rarely turn it on during the week - usually just watch movies on the weekend. I'd much rather be reading. ;-)

 

[SteelWeaver]

"I have seen the dinner table fights before..."

lol. Me too - Catholic - but there was always enough food - I didn't like meat, and my siblings didn't like veggies, so it worked out very well

My brother was hyperactive as a kid, and allergic to everything, so my mom refused to buy anything that was canned, bottled, had colouring, sugar, preservatives, etc etc. And we didn't have TV in SA when I was very young, and when we finally got it, the programming was so boring it wasn't worth watching anyway.

As for intelligent and educated people solving the world's problems - the way I see it, if we can put people on the moon, mine the ocean beds for diamonds and oil, build a space station in which people can live for months on end, write alphabet letters with atoms, make machines that can compute billions of calculations per second, make IMPLANTABLE controlled dose drug chips, put a ranging rover on the surface of MARS, make bombs that can blow up the whole planet, then SURELY a little bit of ingenuity could figure out how to get people to eat healthily. If a fraction of the cash that certain governments spend on "defense" could be pipe-lined to educational projects, we'd have the first leg up.

I personally think social control isn't as hard as everyone seems to think it is - look how many people believe the FDA's food pyramid is OK. Organised religion. The media. We're ALL stuck in the/a box, no matter how much we like to think we're not. It's DIFFICULT to change ideas that one grows up with. Even if one doesn't SUBSCRIBE to those beliefs anymore, they're still there, deep down, whispering in your brain. SO, catch people young.

And even if I'm completely on the wrong track, at least I'm not complacent. Idealism and drive are better than just accepting stuff because it seems too big to change.

So let's get as many compounds as possible and toss them as hard as we can at all the neurotransmitters, receptors, peptides, etc that we can. Maybe we'll find something that not only makes dieting easier, but makes sugary foods etc unpalatable. AND helps build LBM. Whoa!