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Paleoanth
Fri, Jul-07-06, 05:52
http://www.pnas.org/cgi/content/abstract/103/17/6676

Abstract:

Stephane Gesta*, Matthias Blüherhttp://www.pnas.org/math/dagger.gif, Yuji Yamamoto*, Andrew W. Norris*, Janin Berndthttp://www.pnas.org/math/dagger.gif, Susan Kralischhttp://www.pnas.org/math/dagger.gif, Jeremie Boucher*, Choy Lewis*, and C. Ronald Kahn*,http://www.pnas.org/math/link//Dagger.gif

*Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215; and http://www.pnas.org/math/dagger.gifDepartment of Internal Medicine III, University of Leipzig, 04103 Leipzig, Germany





Obesity, especially central obesity, is a hereditable trait associated with a high risk for development of diabetes and metabolic disorders. Combined gene expression analysis of adipocyte- and preadipocyte-containing fractions from intraabdominal and subcutaneous adipose tissue of mice revealed coordinated depot-specific differences in expression of multiple genes involved in embryonic development and pattern specification. These differences were intrinsic and persisted during in vitro culture and differentiation. Similar depot-specific differences in expression of developmental genes were observed in human subcutaneous versus visceral adipose tissue. Furthermore, in humans, several genes exhibited changes in expression that correlated closely with body mass index and/or waist/hip ratio. Together, these data suggest that genetically programmed developmental differences in adipocytes and their precursors in different regions of the body play an important role in obesity, body fat distribution, and potential functional differences between internal and subcutaneous adipose tissue.

Covered with video here:

http://www.sciencentral.com/articles/view.php3?article_id=218392805&cat=1_3

Belly Fat Genes

Are there stubborn places on your body that are the last to show any weight loss from a diet and the first to show weight gain? It turns out, you can blame your genes. As this ScienCentral report explains, researchers studying diabetes have located three genes that dictate where your body stores fat.

Diabetic Risk

Ronald Kahn (http://www.joslin.org/847_1066.asp), president of Boston's Joslin Diabetes Center (http://www.joslin.org/), and his team have identified genes that correlate to where our bodies store fat. He said that, "They're fundamental genes" that are among those that map out how we should grow. He explained that these developmental genes, "tell us that our head should be at one end and that our feet should be at the other ... and these genes also determine both potentially how much fat we have and where that fat is deposited."

Kahn says fat location is important in diabetes research because, "Fat that is located in our belly, what we call central obesity, makes us more prone to diabetes than fat located elsewhere in our body, like our hips or thighs." Kahn says it's because, "This fat creates more insulin resistance…[and]…that insulin (http://www.biostat.wustl.edu/overview/Inthegenes.html) is the major hormone that controls our blood sugar."

Writing in Proceedings of the National Academy of Sciences (http://www.pnas.org/cgi/content/abstract/103/17/6676), Kahn says he and his team found this connection by studying fat in both mice and in people.


Kahn says, We're very excited about this insight into obesity and body fat distribution because this is the first time we've ever had a clue as to how these aspects of our body are so fundamentally determined with these early developmental genes."Kahn and his team started by taking fat from various places in mice. He said, "We used a technique called DNA chips (http://www.gene-chips.com/) to look for the difference in the activity of the genes" in these areas. Kahn says while they did find differences in activity, "The question was, would this be the same for humans?" He says they were able to obtain fat samples from people who were undergoing surgery and examine their fat, as well. He says, "For three of these genes, the activity level of the gene could help us...correlate...with the level of obesity and where the fat was deposited.

Kahn sees two possible uses for the research. The first, he says, "Would be to be able to tell individuals in advance that they are at higher or lower risk so that they might be more attuned to doing the kind of lifestyle modifications that it takes to stay lean and healthy." The second, he says, "Would be to look at the possibility to look at new targets for therapy. Maybe some of these genes could become targets for drug therapies in the future, although at the present we don’t have drugs that are targeted to these genes." He cautions that because these are developmental genes, the challenge will be to target only the fat production. He says if we can do that, "Then we'll really have something that will be a very, I think, novel and new way to think about improving the health of people everywhere."

This study appeared in the April 14, 2006 online edition of Proceedings of the National Academy of Sciences (http://www.pnas.org/) and was funded by the National Institutes of Health (http://www.nih.gov/), the American Diabetes Association (http://www.diabetes.org/home.jsp), the Diabetes Genome Anatomy Project (http://www.diabetesgenome.org/) and the Deutsche Forschungsgemeinschaft (http://www.dfg.de/en/).



(http://javascript%3Cb%3E%3C/b%3E:PopWindow2%28%29) by Jack Penland

LC FP
Fri, Jul-07-06, 21:47
He cautions that because these are developmental genes,

Yes it would be novel to consider preventing obesity by giving drugs to children, infants, fetuses or maybe embryos.

There are a lot of Dr. Kahns we have discussed on this board. I think he is one of the nuttier ones.

Wyvrn
Mon, Jul-10-06, 11:50
I think this is very interesting, though I'd rather see the focus on how to control the expression of these genes with maternal diet rather than drugs.

Wyv

ceberezin
Mon, Jul-10-06, 12:22
Kahn says fat location is important in diabetes research because, "Fat that is located in our belly, what we call central obesity, makes us more prone to diabetes than fat located elsewhere in our body, like our hips or thighs." Kahn says it's because, "This fat creates more insulin resistance…[and]…that insulin is the major hormone that controls our blood sugar."
There is evidence that visceral adipose tissue is hormonally active and that it may contribute to insulin resistance, but to focus on that as a genetic predisposition is totally beside the point. VAT is not the instigator of insulin resistance.

All they have shown is that some people have a predisposition to manifest metabolic syndrome as type 2 diabetes before other manifestations.

LC FP
Mon, Jul-10-06, 17:20
some people have a predisposition to manifest metabolic syndrome as type 2 diabetes before other manifestations.
Right. Others manifest with a heart attack, others with prostate cnacer, etc.

But the AD(diabetes)A doesn't like the term "metabolic syndrome". I think they're afraid that if people with metabolic syndrome are identified, and put on some effective (nutritional) therapy :) , they might run out of diabetics...