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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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June 18, 2008

All The Fat Cells You'll Ever Have - Sort Of

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Posted by Derek

I’ve done a fair amount of work against drug targets for metabolic disorders, so a recent letter in Nature caught my eye. The authors have used an ingenious technique to determine the number and age of the adipocytes (fat cells) that an individual has, and have tracked that cell population year by year.

One thing that comes out is confirmation of the fact that people basically set their number of fat cells during childhood and/or adolescence, and that number is then constant through their adult life. Several subjects in this study put on or took off weight during it, but that made no real difference to their number of adipocytes. And though liposuction does reduce the number of fat cells (by brute force!), they’re back to their original count after three years or so. So weight changes, as other studies have also indicated, are almost entirely due to individual fat cells becoming larger and smaller.

But that doesn’t mean that you’ve got the same fat cells all the way through. Most interestingly, this study found that about 8% of the adipocyte population turns over every year, which is a higher fraction than anyone realized. Half the fat cells in the body, then, have been replaced after about eight years have gone by. That also means that the stable total number results from a balance between adipocyte death and new cell formation, and it would certainly be interesting to know how these are tied together so well. The authors suggest that this relatively high turnover could be a potential target for weight loss drugs. If we could figure out how, say, to keep the fat cell population from being renewed so exactly, their numbers might naturally decrease. (On the other hand, perhaps the rate at which they die would drop to keep the balance – no one knows yet).

So, how do you tell how old a fat cell is, anyway? That’s the ingenious part I mentioned above, and it involves the same sort of techniques used in radiocarbon dating. The amount of carbon-14 in the atmosphere is relatively constant, with a few minor variations over the last fifty thousand years or so. Well, relatively constant except for the 1950s and 1960s, when we as a species reset the counter but good by atmospheric testing of atomic and nuclear weapons. Those tests released a much larger than usual amount of 14C into the world - in 1963 the count had doubled over normal background - and that's since cycled into the biosphere through uptake by plants and other living creatures.

That process has sent the atmospheric levels of radioactive carbon down steeply over the years, but there’s plenty of signal to detect, and we know just how much it’s gone down every year. In effect, every year of the last 50 or 60 has an anomalous carbon-14 reading, and each one is unique and vintage-dated. We take up the carbon through our food, and as a cell is formed, the particular carbon isotope signature of your body at the time is in all its parts. Many of these are recycled constantly – but the DNA isn’t. Extracting the DNA from cells and looking at the carbon-14 levels through mass spectrometry gives you a “production date” stamp for when that cell was born. (See here for a longer discussion of carbon isotope mass spectrometry as it relates to detection of banned steroid hormone use, specifically in the Floyd Landis case. That post, by the way, led to the longest comment thread ever seen on this blog). The same technique is being used for other cell populations as well.

The confirmation that the number of fat cells seems to be set before adulthood also ties in with the obesity trends seen in the general population. The great majority of obese adults were also obese as children, and the great majority of non-obese children do not become obese as adults. What factors set this adipocyte count in a person’s early life, and how many of them are environmental and could be modified, will be very useful to know. . .

Comments (7) + TrackBacks (0) | Category: Diabetes and Obesity


COMMENTS

1. Lothar on June 18, 2008 11:42 PM writes...

Snore... why don't you go back to posting on piting rich against poor and bashing all those lazy chemists who don't know that there's jobs everywhere? I mean the fact that 10,000 chemists were laid off in the last year is only their own fault right?

Hand out some plastic folding chairs and let the games begin!

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2. Karolina. on June 19, 2008 12:33 AM writes...

This post about fat cells was really interesting, as usual. Which is why I start every work day with a peek at your blog. Thanks.

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3. Garote on June 19, 2008 3:06 PM writes...

Hey Lothar: Get a life. >:)

Derek: Interesting clarifications. Who, if anyone, is heading up further research?

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4. Retread on June 24, 2008 1:18 PM writes...

Indeed a fascinating paper. Clearly the massive increase in obesity in the USA in the past 30 - 40 years cannot possibly be genetic -- things just don't happen that quickly in population genetics. For just how rapid and severe the increase has been Google the NHANES study, it's very solid and very depressing data.

However, there is something clearly wrong with our model about obesity and health. Life expectancy has been continually going up and not down, and I would have expected some effect by now. It would be great for the egos of Docs and medicinal chemists to claim that it's our wonderful care and wonderful new drugs at the root of this, but I doubt it.

Not to make this comment too long, but similar work by this (Swedish) group has been overlooked in the general brouhaha about new neuron formation in the brain (which occurs to a far greater extent in animals than in humans). As medicinal chemists you may have heard noises to the effect that new neuron formation in the dentate gyrus of the hippocampus is a/one way antidepressants work.

Well and good, but the earlier 14-C work by this group shows that the amount of new neuron formation in the cerebral cortex (which is what really separates us from the gerbil) is at most 1% over 50 years (or .02%/year). Only 7 patients were used -- born in Sweden between '33 - '73. Sorry--but I've lost the actual citation.

A recent review of neurogenesis in the brain [ Cell vol. 132 pp. 645 - 660 '08 ] acknowledges this work but then spends page after page discussing work in rodents in non-cortical areas

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5. Adam Gross on June 26, 2008 4:16 AM writes...

Fantastic article, this is something I've been very interested in for a very long time. Having personally seen liposuction patients get fat again a few years down the road I knew there had to be a catch.

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6. Robyn Penwell on July 2, 2008 9:43 PM writes...

As a fitness professional I enjoyed reading this informative post. Retreads comments are on the mark, but I have to throw in another idea or two. Though people are living longer, I understand that the bulk of the credit goes to better community and personal sanitation practices. Prescription drugs are keeping over-fat and obese people alive. How many people do you know who would be dead without their blood pressure, diabetes, and cholesterol medications? I read that the average number of retail prescriptions per capita increased from 7.9 in 1994 to 12.3 in 2005*. Our population trends fatter and fatter right along with this prescription trend.
*
Kaiser Family Foundation calculations using data from IMS
Health at http://www.imshealth.com (US Top-Line Industry
Data) and Census Bureau at http;//www.census.gov.

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7. Retread on July 3, 2008 10:13 AM writes...

It would be good for the egos of pharmaceutical chemists and MDs if our great drugs and great care were the Dutch boy's finger in the dike of obesity morbidity and mortality, but the surge in American fatness has been going on now for 30+ years without noticeable effect on longevity or age adjusted mortality. We should at least consider that there is something wrong with our model.

My late grandfather was a hard man. Most immigrants were. My father told me he used to say "people dig their graves with their teeth". He bought the model before there was the model.

Americans don't like to talk about class, but like smoking obesity is largely a class phenomenon. Most readers of this blog are probably not working class (although given American social mobility probably over half have a working class background). Look about you -- how many obese people are there in your job description? Now look at school crossing guards, factory workers (assuming you know any), garbagemen, or convenience store clerks.

It's so sad because it's so unnecessay (assuming the model is correct). It wasn't this way 40 years ago. Again, look up the NHANES studies.

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