Big Boned Fat
Aug 21st, 2007 | By Jonathan Golob | Category: MedicineSee if this makes sense to you:
Weight is an intrinsic trait, determined mostly by our genes. Yet, globally the number of obese people has nearly doubled since 1980–faster than alleles can redistribute in the population.
The amount we eat is strictly controlled by regulatory systems. Each of us is endowed with an energy set-point; forced overeating makes people feel ill, until their weight drops back down. Unless, of course you are obese, where the setpoint is somehow reset to much higher than it should be; eating fewer calories to dip below the new setpoint results in a starvation response from the body, even for people who are massively overweight.
The more overweight you are, the higher your risk for heart attacks, strokes, diabetes, sleep apnea, high blood pressure and even some cancers. Unless you are active and obese; for at least some of these maladies, you’d statistically have a similar risk to sedentary skinny folk.
Confused yet? Mix in all the high emotions that come from questioning who or what is responsible for our increasingly zaftig culture, and it’s a real mess.
So, let’s add one more piece: Your bone and fat cells are talking to one another.
We’ve known for a while that being obese protects you from osteoporosis. A protein made by fat cells called leptin–also essential for regulating feeling full when you’ve had enough to eat–stimulates the bone making osteoblast cells.
The authors of a recent Cell study figured that if fat cells can stimulate bone-producing cells, the bone cells should signal back to the fat, creating a tidy negative feedback loop, where the fat cells stimulate bone producing cells (“We need stronger bones to carry around all this fat!”), and the bone cells inhibit fat formation (“Too. Much. To. Carry. Stop making fat!”)
So, what could be this signal? Bone producing cells create only a handful of distinct proteins, one of which deemed Osteocalcin. Mice lacking the Osteocalcin gene have fat bellies. Very interesting.
In this most recent study, the scientists followed this trail, and found that mice without Osteocalcin are not only fat, but are also glucose intolerant — just like people with type-II diabetes. So, less Osteocalcin, more diabetes-like symptoms.
Don’t take my word for it, here is are some snippets from figure 5 of the paper.
The mice lacking Ostocalcin (in blue) have bigger abdominal fat pads than normal mice (gray).
Compared to normal friends, the Osteocalcin-lacking mice drop their blood sugar much less after being injected with insulin.
And Osteocalcin-lacking mice do a much poorer job of cleaning up after sugar is injected into them.
Ok, great. But how are the bone cells figuring out how much Osteocalcin to release? The scientists went on to knock out a signal receptor only in bone forming cells, Esp. Mice without the Esp receptor have more insulin producing cells (left is normal, right is from a mouse lacking Esp),
more insulin production (gray normal mouse as compared to green or red mice lacking Esp),
and increased sensitivity to insulin (gray normal mouse as compared to green or red mice lacking Esp)
– the anti-diabetes.
So, maybe signaling through the Esp receptor blocks Osteocalcin release; remove Esp and you’d get a flood of anti-fat Osteocalcin, right? The authors tested this idea by also getting rid of only one copy of the Osteocalcin gene in mice already without Esp.
It worked. Mice lacking both were more or less normal. (Holy double negatives, batman.)
So, who knows. Now for some wild speculation: Perhaps stimulating your skeleton is key in preventing diabetes. Certainly bone producing cells in mice can pump out a powerful signal that blocks belly fat, and keeps the blood sugar regulating system humming along. Next time you think about spending the whole weekend on the couch, think about the conversation between your bone and fat cells. Next time you think about spending the whole weekend on the couch, think about the conversation between your bone and fat cells.
Dear Science,
Do you have any citations for the claims made in the first three paragraphs of your post? I’m not necessarily disputing them, just curious about the source.
all best,
. j
I should go and add the citations. Laziness took hold before I converted all the Endnote citations to hyperlinks. Still, you’re right.
Thank-you for reading.
Here is a decent review covering the endocrine regulation of energy balence.
For the claim that weight is genetically regulated, there are many many studies. Among the most recent is one following monozygotic and dizygotic twins to age 18.
The increase in obesity is from WHO and CDC stats. Pretty shocking, eh?
For the strict regulation of how much we eat is mostly from that review, and some seminars I’ve attended at the UW.
The resetting of the endocrine system to maintain a higher weight in Obese individuals was also mostly from seminars.
For the fat-and-fit notion, there are also several studies. One recently demonstated that obese individuals who are active have less visceral fat–the kind of fat that causes the most grief.
Hope this helps.
Dear Science,
Are you even partially concerned about your use of Cell’s figures? I know you will point out the fair use clause related to publishing in general, but you present a lot of copyrighted material here!
It’s a legal and ethical question, right?
From a legal POV, yes I am well within fair use.
Specifically:
1. This is clearly a non-profit educational use of the material.
2. Only a tiny portion of the figures in the paper — this is a Cell paper after all, dense enough to prevent light from escaping — is shown here.
3. If you were going to pay to read the article, what I posted isn’t enough to dissuade you from doing so.
Posting the full PDF would be clearly out of bounds; this is quite mild in comparison.
From an ethical point of view, I’ve clearly cited the source of these figures, and I’ve not claimed credit for the work; this isn’t plagiarism. From a utilitarian point-of-view, I’ve provided publicity for the authors, the study, the field of research, the results and the Journal itself.
Whew. Enough defensive posturing.
My question to you: Isn’t it ethically repugnant to commercially copyright — and prevent the public from accessing for decades — the results of publicly funded research?
hi…
super!…
my niece sometimes uses Fat Pads ~”:
There are some interesting time limits on this article but I don’t know if I see all of them heart to heart. There may be some validity but I’ll take hold opinion till I look into it further. Good article , thanks and we wish more! Added to FeedBurner as nicely
Fantastic web log! As i really really enjoy the simplest way it’s painless with this view and then the facts are well written. We are asking buying and selling domains may perhaps be warned any time a latest article has been. May very well subscribed to the feed of which have to the trick! Possess a pleasant day time!
hello there and thank you for your info – I’ve certainly picked up something new from proper here. I did however expertise some technical points using this web site, as I experienced to reload the web site lots of occasions prior to I may get it to load correctly. I have been wondering in case your web host is OK? Not that I am complaining, but sluggish loading cases instances will very frequently affect your placement in google and can harm your quality rating if ads and ***********|advertising|advertising|advertising and *********** with Adwords. Anyway I’m including this RSS to my email and can glance out for much more of your respective intriguing content. Ensure that you update this again very soon..