[Meg]

I thought of this thread right away when I came across a clinical trial that's currently recruiting participants to study the effects of leptin supplementation for the reduced obese:

Purpose

Our previous studies have demonstrated that there is substantial metabolic opposition to the maintenance of an altered body weight. Leptin is a protein secreted by fat cells and the circulating concentrations of leptin are directly proportional to fat mass. Leptin-deficiency is associated with severe obesity in rodents and in humans and the obesity is relieved by leptin administration. These studies examine the hypothesis that some of this metabolic opposition cto the maintenance of an altered body weight can be relieved by restoring circulating concentrations of the hormone leptin to the same range as at usual body weight in subjects who are maintaining a reduced body weight. The basic design of this study is to observe subjects at a 10% reduced body weight and then again at that reduced body weight while receiving physiological leptin supplementation.

http://clinicaltrials.gov/ct/gui/sho...73242?order=14

The trial is being sponsored by Columbia Medical School, which is where Dr. Leibel (discussed in my original post) conducts his research into obesity and metabolism. I'm sure his lab is associated with this project.

Wouldn't it be wonderful if some day we could take something like leptin that would make maintenance a little easier? Not a magic pill, but simply adding back something that's missing in our reduced obese bodies?

[Mel]

bump- this was getting lost

[RobertW]

Interesting thread. I happen to work at Columbia P&S, although I am in a different department (Microbiology) and I am not familiar with Leibel's work. I haven't seen any solicitations for his studies here, but i would have volunteered if the price was right.


Regarding the lower maintainance calories for the formerly obese: isn't that thought to be tied to the activity level as well? I seem to recall a paper in "Science" a year or two back showing that obese individuals expended much less energy than normal volunteers wearing weights to simulate obesity. Fat people were found to be much more ecconomical in their movements.

Unless our body temperatures are lower, nervous systems less active etc. I don't see why we would need less energy than naturally thin people of the same size unless we didn't move as much.

[Meg]

It may not seem logical, but Leibel was crystal clear that this is NOT related to activity levels, as you speculate. It is a permanent slowdown on a metabolic level that happens to reduced obese. We burn 15-20% fewer calories doing the same activities as a never obese person.

I have an article discussing this further from the December 3 issue of the Economist that I'll try and post about tomorrow. In the meantime, try a MedLine search on 'Leibel' and 'leptin' and you should find a ton of further information.

[RobertW]

From the Columbia website:

Rudolph Leibel, M.D.
Dr. Leibel is the Chief of the Division of Molecular Genetics and the Co-Director of the Naomi Berrie Diabetes Center. He is a Professor in the Departments of Pediatrics and Medicine.

He is NOT the Molecular Genetics department chair but a "Director" of a very small division (two professors and one instructor, plus some fellows and students). Not really even a large laboratory. I hope he was not overstating his credentials.

Originally Posted by Meg

It may not seem logical, but Leibel was crystal clear that this is NOT related to activity levels, as you speculate. It is a permanent slowdown on a metabolic level that happens to reduced obese. We burn 15-20% fewer calories doing the same activities as a never obese person.

What a surprise; a leptin researcher thinks leptin is the most important factor.

I only really see one paper where he is addressing the proposed mechanism for greater efficiency by "formerly obese" subjects and he is claiming that leptin levels correlate with "muscular efficiency".

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

[Meg]

I'm curious -- Robert, you're a scientist, right? Just because you personally may not agree with research results and conclusions, do you generally bash and/or belittle other scientists and their research with snarky little comments?

Research into weight loss maintenance and leptin isn't new or radical. This came out last month:

In a study appearing in the December 1 issue of the Journal of Clinical Investigation, Michael Rosenbaum and colleagues from Columbia University College of Physicians and Surgeons show that body weight is regulated by coordinate metabolic, neuroendocrine, and autonomic systems that act to actually restore fat mass in individuals attempting to maintain their slim new figure. The authors suggest that our bodies interpret the weight-reduced state as one of relative deficiency in the hormone leptin.

To test their hypothesis, the authors administered "replacement" doses of leptin to lean individuals that had recently lost weight as well as to obese individuals. The authors found that most of the metabolic, neuroendocrine, and autonomic changes that oppose the maintenance of a reduced body weight were actually reversed once circulating levels of leptin were restored to levels that were present prior to weight loss. These mechanisms lie at the center of why more than 85% of obese individuals that have lost weight eventually relapse.

These findings suggest that therapeutics directed at the leptin signaling pathway may, pending longer studies, assist in the maintenance of reduced body weight.

The full text can be found here. http://www.jci.org/cgi/content/full/115/12/3579

The reason that I summarized the lecture for the Maintainers Forum is that these conclusions ring so true for many of us struggling to maintain a goal weight. You're still in the losing phase and haven't yet experienced maintenance. In contrast, we're maintaining and LIVING the issues of calories and exercise and why it can be so difficult to maintain a reduced body weight -- why it feels like our bodies are fighting to be fat again.

Of course, you personally can choose to accept or reject any of these findings. However, the findings of these researchers make total sense to me and help me to further understand what I'm dealing with as I work everyday to keep the weght off. Without an explanation of what is happening in my body on a biochemical and hormonal basis, I would be baffled and frustrated by the challenges of maintenance. Now that I know what I'm up against, I can deal. As Mel has said, it may be depressing but it's reality.

[RobertW]

Originally Posted by Meg

I'm curious -- Robert, you're a scientist, right? Just because you personally may not agree with research results and conclusions, do you generally bash and/or belittle other scientists and their research with snarky little comments?

I bet you don't spend a lot of time around scientists


I am not belittling him; all researchers are going to champion the importance of their own work. It is up to less biased people to sort it out.

If he gives a seminar or participates in a dataclub around here I would be very interested in discussing his work with him.

Research into weight loss maintenance and leptin isn't new or radical. This came out last month:

The full text can be found here. http://www.jci.org/cgi/content/full/115/12/3579

The reason that I summarized the lecture for the Maintainers Forum is that these conclusions ring so true for many of us struggling to maintain a goal weight. You're still in the losing phase and haven't yet experienced maintenance. In contrast, we're maintaining and LIVING the issues of calories and exercise and why it can be so difficult to maintain a reduced body weight -- why it feels like our bodies are fighting to be fat again.

Of course, you personally can choose to accept or reject any of these findings. However, the findings of these researchers make total sense to me and help me to further understand what I'm dealing with as I work everyday to keep the weght off. Without an explanation of what is happening in my body on a biochemical and hormonal basis, I would be baffled and frustrated by the challenges of maintenance. Now that I know what I'm up against, I can deal. As Mel has said, it may be depressing but it's reality.

That is the same paper I posted a link to above. Does it really make sense to you that leptin affecting the "efficiency" of muscles being the MAJOR mechanism rather than one of several contributing factors?

It makes little sense to me from an evolutionary perspective. Why isn't everyone using this leptin mechanism to conserve energy all the time unless there is some hidden price? Calories restriction mode involves reproductive shut down, and other dramatic changes. What price is there in his "increased efficency"?

I don't follow this field closely, but my recollection was that leptin had very dramatic effects in mice but not so dramatic in humans.

IMHO, the big genetic factor for most obese individuals is going to be tied into appetite. Feeling satiated by your maintainance calories is what is going to keep you from spontaneously gaining weight in a calorie rich environment, not whether or not that maintainance level is 1200 vs 1400 cal per day. If leptin is the key to the body's set-point, than I suspect that its role in determining how full we feel on X-amount of food is what is really important.

Why do maintainers struggle? Most likely because, unlike normal people, they don't feel full on their maintainace calories. My appetite is ~5-6,000 cal/day as a fat person. Will that change as a maintainer when my BMR is more like 3-4,000 cal at my goal weight? I am guessing not, thus there will always be a certain tendency to gain unless I exert some control. Whether or not leptin is making my muscles "more efficient" is a minor point, even if his data is both correctly interpreted and significant.

Meg, why would you think that getting thin would "cure" you of a tendency toward obesity? Of course their is an underlying medical basis to obesity, I am just not sure the above paper is making a good case for the precise mechanism.

[Meg]

Originally Posted by RobertW

Meg, why would you think that getting thin would "cure" you of a tendency toward obesity?

Guess you've never read anything that I've ever posted about maintenance ... too funny!

[RobertW]

Originally Posted by Meg

Guess you've never read anything that I've ever posted about maintenance ... too funny!

Sorry, I am not a maintainer. I linked here from another forum.

Do you really think that if you could only consume 16% more calories without gaining it would make that big of a difference? I don't find that figure particularly daunting.

What would scare me is if my appetite increased to the point I wanted to eat 10,000 Cal a day till i gained back 150#. I know I can deal with a 6,000 Cal/day "habit" because I have one right now. 3,000 Cal BMR vs. 3,600 Cal of appetite looks pretty easy to me.

[Mel]

Do you really think that if you could only consume 16% more calories without gaining it would make that big of a difference? I don't find that figure particularly daunting.

That's because you will be able to maintain on 3000-3600 calories. Even for someone your size, you can make that translate to a lot of food. I maintain on 1400 calories and gain on 1500. Somewhere around 1300 I lose. I'm VERY active, have more muscle than most women my size, and am almost always hungry. Not just "head hungry". I go to bed most nights with my stomach rumbling. You bet 16% more calories would make a difference to me!

Mel

[RobertW]

Originally Posted by Mel

Not just "head hungry". I go to bed most nights with my stomach rumbling.

It does sound like your body does want to be heavier.

Did you feel that way when you were losing? I don't although I generally don't eat between 1 PM and 6AM and I am consuming (for me) a very modest 2,000-2,500 Cal/ day. I am definitely just "head hungry".

I was wondering if most people hit a certain bodyfat % and their appetite gets fired up again. If so, the extra 16% wouldn't stave off the hunger; that won't go away until you get fatter.

While I am shooting for 10% bodyfat, I am okay with maintaining at 15-20% if I am going to have to fight tooth and nail to stay that low. Most men my age (41) are fatter than that.

I am a really large person which is fine; I just want to be big rather than fat for a change.

[Mel]

I was always hungry while I was losing, and nothing has changed. I know my body wants to be heavier, but I don't like it heavier. The bodyfat level at which I'm attempting to maintain is low for a woman my age (51).l Aside from personal cosmetic issues, I'm in the fitness and sports nutrition business. I feel like I need to look like I "walk the walk".

Mel

[Ilene]

Originally Posted by Mel

I feel like I need to look like I "walk the walk".

You know what Mel, I actually really LIKE looking like I walks the walk.... Mel, I think you jinxed me, since my body composition is changing, not necessarily the scale moving, I hungry ALL the time lately... Doesn't matter what I eat or how dense and filling it is I am hungry about an hour and a half later ... I think our muscles are just absorbing the food and nutrients, do you think that makes sense??

[RobertW]

Yes, one of my initial weightloss goals is to lose enough fat so that I actually look like I lift weights.


Regarding genetics and obesity, I think the leptin story shows us that the genetic basis of obesity is much more complicated in humans than in mice, and the ultimate answers are more likely to come from the human genomic projects. I am not sure the US project included any obese individuals, but I am certain the Icelandic project does because they are sequencing ALL of the genes in the Icelandic population.

Decode

I see that they have already found a new "fat gene":

*
DeCode Finds A Fat Gene
Matthew Herper, 09.30.03, 1:36 PM ET

NEW YORK - DeCode Genetics announced this morning that it had found a gene linked to obesity, prompting a milestone payment from its partner Merck. The tiny Icelandic genomics company's shares shot up 15% to $4.90 in Nasdaq trading, even though neither the amount of the milestone payment nor much information about the gene was disclosed.



DeCode (nasdaq: DCGN - news - people ) said in its statement this morning that one form of the gene predisposed people to become fat, while another predisposed them to be thin. "Obesity and thinness are two sides of the same coin, and with our partners at Merck we are working to identify the best targets for therapeutic intervention within this pathway, as well as compounds that are effective against these targets," DeCode Chief Executive Kari Stefansson said in the statement. "This is an important step toward developing new drugs that can treat obesity, perhaps by utilizing the body's own mechanisms for promoting and maintaining thinness."

DeCode provided few further details about this discovery. That's not unusual. But more information may emerge at some point in the future. For example, DeCode last week published a paper describing a gene related to stroke in the scientific journal Nature Genetics. A similar paper on the fat gene may be in the works.

Finding the gene would be only the first step. Developing a drug based on genomics is no easy task. Millennium Pharmaceuticals (nasdaq: MLNM - news - people ) and Abbott Laboratories (nyse: ABT - news - people ) at one point were co-developing an obesity drug, but that product, MLN4760, apparently was mothballed. In August the two companies scrapped their alliance, which had been started in 2001 to use genomics to look for drugs to fight diabetes and obesity.

When Merck (nyse: MRK - news - people ) and DeCode announced their partnership in September 2002, the companies said the deal had a potential value of $90 million to DeCode even before royalties with new drugs are included. DeCode also has an alliance with computing giant IBM (nyse: IBM - news - people ) to sell gene-sleuthing software it developed.

Link: http://www.forbes.com/2003/09/30/cx_mh_0930decode.html

Too bad the partner is Merck; I have no faith in their product safety.

[clarabr]

Hi!

I haven't read the whole thread, but I just wanted to say that I can't relate to the lower maintenance calories for the "reduced obese". Maybe his findings really only apply to former obese people, and not to those of us who were only overweight, like others have pointed out. Personally, I never had to eat that little or exercise that much to maintain my 37-lb loss (I maintained that for 5 years, then regained 10 and have maintained for the past 4, but I swear this year I'll get rid of those 10!). Anyway, I gained those 10 because I ate like a pig, I *cannot* blame my body for it. I maintain easily at 2100-2200 cals/day.

Is it ok for me to post here? Or should I stick to the support forum, since I'm trying to lose again? I'm so excited to post! I've been lurking for years!