The MakeMeThinner Support Forum

[LongWay2go]

This information provided from the Salk Institute "News" page located at http://www.salk.edu/news/releases/details.php?id=104

Marathoning Mice Could Have Olympian Effects on Obesity

August 24, 2004
LA JOLLA, CA — A molecular switch known to regulate fat metabolism appears to prevent obesity and turns laboratory mice into marathon runners, a Salk Institute study has found.

The discovery of the switch could lead to treatments for obesity and disorders associated with it, such as heart disease and type 2 diabetes. The study, led by professor Ronald Evans and his postdoctoral fellow Yong-Xu Wang, appears in the September issue of the Public Library of Science Biology journal (PLoS Biology). Evans is also an Investigator of the Howard Hughes Medical Institute.

Evans, Wang and team discovered that activation of the switch, a receptor called PPAR-delta, increases the rate at which the body burns fat. This makes PPAR-delta an exciting potential target for drugs that treat diabetes and lipid disorders.
The team produced a genetically engineered mouse endowed with the activated form of PPAR-delta in its skeletal muscles. The result was a dramatic increase in "non-fatiguing" or "slow twitch" muscle cells and a mouse capable of running up to twice the distance of a normal littermate without training.

By expressing genes for an activated form of the receptor PPAR-delta, we created a mouse that could, compared to normal mice, run marathons, said Evans. The activated form of PPAR-delta produced muscle fibers that enhanced endurance exercise."
By turning on PPAR-delta, the team had produced highly efficient muscle fibers that burned fat more rapidly. As a result, the mice were almost unable to gain weight even in the absence of exercise.

"These muscles also provided resistance to obesity, despite the level of exercise," said Evans. "By manipulating this receptor, it is possible to design treatments that change our muscle makeup and help resist obesity and associated metabolic disorders.

To test the concept, Evans and his team treated normal mice with an experimental drug called GW501516 that activates PPAR-delta. These mice also expressed genes for slow-twitch muscles and gained less weight when given a high-fat diet. This drug is now in the earliest stages of being tested on people for its effects on obesity and other disorders of fat metabolism such as high blood cholesterol.

This experiment underscores the importance of metabolism in fighting obesity and improving fitness, said Evans. Activating the PPAR switch may prevent physical fatigue and enhance the quality of exercise, which may lead to a new class of drugs to promote weight loss and treat diseases arising from an overweight population.

The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. Jonas Salk, M.D., founded the institute in 1960 with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.

[hawaiiwhatnot]

Okie dokie! (Rolling up my sleeve) Where do I sign up?

BTW Gerald, 23.5 lbs in 2 weeks? WAY TO GO BRADDAH!!!!

Camille

[LongWay2go]

No kidding, they can poke me with needles or whatever, just make me skinny and let me eat anything I want!

Thanks Camille!

[Landylue]

I thought I had tried just about everything in my 55 long years, but having my PPAR switch activated is definitely not one of them. I'm with Camille, where in the world do I sign up?

Hmmmm, to be honest, though, Gerald, I heard this weekend on NPR that a full 60% of the population of Africa is HIV positive. I think I would rather these good doctors focus more on a disease that is killing off an entire continent, or curing muscular dystrophy, or cancer than a drug that would melt fat off of people like me--us. We're here because of the choices we've made over our lifetime, my friend. We can CHOOSE to get better anytime we want. These other people can't.

We are all so very blessed, Gerald.

By the way, your dancing Spiderman is delightful!

Landylue

[LongWay2go]

Hi Landylue,

Thanks! Ask Unca, I worked hard to get spidey down to avatar size!

I have to agree with you to some degree. HIV is a major world problem and I think education is just as important a tool as a "cure". However, to the best of my knowledge, obesity and obesity related illnesses are the #1 killers in the world today and are therefore just as important. Research and education are our two weakest areas and we need to be spending 100x the money that we do to fund research and educate our entire population. We need free healthcare in this country AND the world, and our schools should have a required nutrition course for our youth. Our representatives do a lot of talking, but we need action. We are blessed to be the richest nation in the world yet we cannot manage to take care of our elderly or educate our children.

I'm not arguing your point about HIV though, don't misunderstand that! In fact, we (being my company and me personally) are a huge annual contributor to a local food kitchen called Community Servings who's purpose is to provide daily meals to people living with AIDS/HIV. We also sponsor the annual Massachusetts Red Ribbon (AIDS/HIV research funding) ride every year. In fact, recall a couple of weeks ago I was gone for a couple of days? That's because I was transporting a van full of cyclists to Western MA for the three-day ride so they would not have to take a bus. I'm with you all the way, not just in spirit, but financially as well!

Remember too that I lost my mother, father and two of my best friends to obesity related illnesses, and that drives me.

-Gerald (aka Spidey to be!)

[Nancy]

Spidey ~

What an interesting post. Thanks so much for putting the link on for us.

The team produced a genetically engineered mouse endowed with the activated form of PPAR-delta in its skeletal muscles. The result was a dramatic increase in "non-fatiguing" or "slow twitch" muscle cells and a mouse capable of running up to twice the distance of a normal littermate without training.

By expressing genes for an activated form of the receptor PPAR-delta, we created a mouse that could, compared to normal mice, run marathons, said Evans. The activated form of PPAR-delta produced muscle fibers that enhanced endurance exercise."
By turning on PPAR-delta, the team had produced highly efficient muscle fibers that burned fat more rapidly. As a result, the mice were almost unable to gain weight even in the absence of exercise.

In a sense, MF has done just that for me! I may not have twitchless muscle cells but I lost weight (135 pounds of yucky flabbage) with virtually no exercise - yep, in the absence of exercise, MF burned off the flab and my muscles became more defined.)

I am NOT advocating that you folks do not exercise. I am just saying that I really did not do anything special in terms of exercise like so many of you are doing. You are to be commended for hauling it down to the gym and sweatin' it off.

I hate to sweat and I hate to get sweaty. I am an ACTIVE woman, do not sit around much (well, I didn't used to park it much until my email volume and the Forum began to take up more of my time!) and yet because of the research and pharmaceutical qualities of MF, it causes our bodies to function in the way they were meant to be. MF is an engineered product that is so easy to prepare and tastes pretty good. It certainly burned off my fat! Whatever it does and however it works, I love it!

Last night I went over to a friend’s apartment and used his pool to check out my fins, mask and snorkel and to practice snorkeling. A couple of years ago I would NEVER have done that – worn a bathing suit in front of people I know. Last night, however, I wore my leopardy print suit with a leopard print sarong IN THE CAR to his place. I walked right up to his door, rang the doorbell and walked through a maze of cars AND people IN MY BATHING SUIT during semi-daylight hours! I swam and snorked and froze my bippy off. I need insulation if I am to swim in an unheated pool! I crawled into the hot tub with Terry for a few minutes and then I wore my bathing suit home! All Because I Can!

I may not run marathons like our genetically engineered mouse friend above, but compared to how I used to live my life, I run circles around that former Flabulous lady every day.

It is marvelous that research is continually working behind the scenes to make our lives easier. You know you dear people do so much individually as well as collectively to enrich our lives here at MakeMeThinner. You are full of wonder and we truly appreciate each one of you! Here’s to your success!

[LongWay2go]

Leopard Woman wrote:

A couple of years ago I would NEVER have done that – worn a bathing suit in front of people I know. Last night, however, I wore my leopardy print suit with a leopard print sarong IN THE CAR to his place.

Hm, maybe when I "get there" I'll get a leopard print speedo, just for Mike's amusement! ROFL!!!

-Gerald

[Nancy]

Oh yeah, Spidey in a Speedo!

Leopard Print!! Yeah!

Mikey, your Speedo has flames, Man!

[Sylvia]

First tights, now speedos? All I can say is YUCK! And remember, just because you CAN doesn't mean that you SHOULD! Now a nice pair of tight jeans - that's another story...

[LongWay2go]

All in good fun, Sylvia! Just because I CAN doesn't mean I WOULD inflict that pain on the world! LOL

-Gerald

[Landylue]

I'm with Sylvia. There's nothing more pleasing to the eye, at least MY eye, than a long-legged dude 'covered up' in semi-tight blue jeans wearing a flannel shirt. Oh, alright, so in my vision the shirt isn't buttoned, but he's covered up for the most part. . .

Anyway, guys, never one to be out done by a slow-twitch mouse, I ventured out today (after dark--I'm not as brave as Nancy) and jogged for the first time in YEARS! I only jogged a half mile before my lungs started burning, but I was shocked I made it that far. I also know that if I can do a half mile now, and if I work on it a little each day, I'll be able to run a 5K on Thanksgiving morning in downtown Dallas--the annual Turkey Trot. I haven't done that since the kids were in high school.

That's my goal, and I'm stickin' to it! To be in shape enough to run a 5K by Thanksgiving would really be something to be thankful for.

That, and the people on this forum.

Gerald, you sound like a pretty awesome individual.

Landylue

[hawaiiwhatnot]

Landy- Kudos to you for getting out and jogging for the first time in years! That's tough to summon up the discipline to get out there - in the daylight or dark (very cute-dashing around in the dark). Good for you, and as I've said before, anyone who aspires to do marathons has my complete respect.

Gerald- Well personally I don't think the Speedo would be bad at all as long as you're wearing that BMW around it. Just kidding - we're all gonna look great in whatever we wear! You ARE a special person - if only the world were full of people as helpful...

Camille

[Nancy]

Landy ~

What a great goal you have! You will be there, I'm sure!

You are in super shape if you were able to run a half mile! I am impressed!

As awesome and lithe as Leopard Woman is, she does not run. She has a bad hip and running is not something she typically does - well under normal conditions she does not run unless she HAS to - like when she has to run to hop on a trolley car in San Francisco, or run to catch a flight after meeting MakeMeThinner Forum Friends at the airport, or run to a sale at Nordstrom's! Hee hee!

Landy, you may be running in the annual Turkey Trot but my Thinning Friend, you definitely are NOT a turkey! You will be Hot to Trot when you are at your goal weight. We will be cheering you on as you run for the finish line! Because you can!

What an inspiration you are to us.

[Simmshe]

This turned out to be a funny post ! Personally, I don't want the words "tight" or "snug" in the same sentence with my boyfriend's wardrobe! Don't like baggy, baggies, but I do like a little leggy look on men .

Now, about the topic at hand, I'm with you Landylue about the AIDS pandemic in Africa. This is a very important issue, as is obesity, but the difference between the two is the modes of treatment (which is absolutely abysmal and/or nonexistent in many African countries). Oh, and the AIDS statistic you quoted isn't accurate--only about 7.5% of adults in sub-Saharan Africa are HIV positive, with another 2 million (or so) children being infected. But comparing that rate to the rate on other continents, North America, for example, which has a 0.6% infection rate, it's easy to see how drastic the problem is in Africa. I think the stat that you heard was that about 70% HIV infected people live in Africa (particularly Sub-Saharan Africa). Unfortunately though, a couple of southern African countries have HIV infection rates approaching 40%, but then there are other African countries with only 1-5% infection rates. Whoa, 60%, they would have to quarantine the whole continent!! Anyways, didn't mean to lecture--this is just one of my social issues of interest, so I wanted to clarify this .

You know, I recently read two articles about obesity in this country--one article that was in Time magazine and one that was in National Geographic. These articles broke down the science of fat/obesity--in fact, the National Geographic article (which was on the cover) was titled "Heavy Cost of Fat." Both articles went on to talk about new research studies going on, promising medications, and current methods of losing weight. Of course, we all know that with obesity in some people is genetic, and this is where science is doing most of their studies--trying to figure out ways to manipulate the genes of obese, or potentially obese, people. Some people have severely limited metabolism function, which medication will be beneficial; while others just have slower than average metabolisms (and/or fat genes to boot), in which exercise and normal eating can help them. Anyways, the point that I thought was so poignant was the bottom line from scientist. I can't remember which article ended this way, but one of the obesity researchers said that while all of these medications are on the horizon, the best tested and proven method of all was this: eat less and exercise more. It's not this simple of course, but this always seems to be the bottom line. There is oodles of money going into obesity research and educational efforts to help us get our waistlines in check. But there are dirt poor, uneducated HIV infected people in Africa who can't even get medication that would extend their lives. They only have a couple of years or so to wait for a cure.

Obesity-related diseases are definitely on the rise, though not the leading killer of people world-wide (just in the U.S. where obesity-related diseases are about to surpass smoking and all other causes of preventable deaths). Anyways, these are both important issues, but I believe that overhauling our food market (toooo much garbage--no wonder children are becoming fatter, and schools have actually cut down on P.E. time!), overhauling portion sizes in restaurants, and EXERCISING (man, we are LAZY--I have been on a public bus here and seen people get on the bus just to ride four blocks!) will go a long way in our battle of the bulge. These measures alone will be especially helpful with just getting the overweight-but-not-obese people off of the statistic list. Now HIV/AIDS is a different story. When you have a small country (like Swaziland) where 40% of the adult population is HIV positive, this country's entire population will be wiped out in a matter of generations if this trend is not reversed soon. Education doesn't work as well in poor countries where sexual violence, gender inequalities, and poverty are so prevalent--57% of all HIV positive people in Africa are women. Anyways, I could go and on--off of my soapbox now . These are both important issues, but I think you all get my point .

Obviously, this is something I'm passionate about--didn't mean to go on so much! Oh well, there was a little HIV/AIDS lesson for anyone who didn't know details ! Time to take my drowsy butt to bed--it's 3:00 AM .

Sheryl