Wednesday, July 23, 2014

In Memorium: Albert (Mickey) J Stunkard

Stunkard twinsAs I spend my days at the 9th Canadian Obesity Network’s Summer Bootcamp for young trainees from Canada and around the world, I was saddened to learn of the passing of Mickey Stunkard, clearly one of the biggest names in obesity research – at a healthy age of 92.

With well over 500 publications to his name, Mickey is perhaps best known for his twin studies showing that the body weight of adopted identical twins reared apart resembles each other and that of their biological parents rather than the weight of their adoptive parents.

This work helped establish the basis for much of the genetic work on obesity that followed, clearly showing that differences in body weight between two individuals are much more accounted for by their difference in genetics than by differences in their “lifestyles”.

These findings were often misused in “nature vs. nurture” debates, an issue that serious scientists have long laid to rest in light of our current understanding that the two cannot be discussed separately, simply because genes and lifestyle interact on virtually every level – from molecules, to cells, to behaviours.

Here is what one obituary had to say about Mickey:

“He surveyed obesity treatment studies in the late ’50s and found that the nation’s diet programs could claim only a 2 percent success rate. He was an early advocate for the use of bariatric surgery to induce weight loss. He also published the first modern account of binge eating in obese individuals.”

I have had to pleasure to often hear him speak at conferences.

He will be dearly remembered.

Kananaskis, AB


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Wednesday, June 18, 2014

4th Canadian Obesity student Meeting (COSM 2014)

Uwaterloo_sealOver the next three days, I will be in Waterloo, Ontario, attending the 4th biennial Canadian Obesity Student Meeting (COSM 2014), a rather unique capacity building event organised by the Canadian Obesity Network’s Students and New Professionals (CON-SNP).

CON-SNP consist of an extensive network within CON, comprising of over 1000 trainees organised in about 30 chapters at universities and colleges across Canada.

Students and trainees in this network come from a wide range of backgrounds and span faculties and research interests as diverse as molecular genetics and public health, kinesiology and bariatric surgery, education and marketing, or energy metabolism and ingestive behaviour.

Over the past eight years, since the 1st COSM was hosted by laval university in Quebec, these meetings have been attended by over 600 students, most presenting their original research work, often for the first time to an audience of peers.

Indeed, it is the peer-led nature of this meeting that makes it so unique. COSM is entirely organised by CON-SNP – the students select the site, book the venues, review the abstracts, design the program, chair the sessions, and lead the discussions.

Although a few senior faculty are invited, they are largely observers, at best participating in discussions and giving the odd plenary lecture. But 85% of the program is delivered by the trainees themselves.

Apart from the sheer pleasure of sharing in the excitement of the participants, it has been particularly rewarding to follow the careers of many of the trainees who attended the first COSMs – many now themselves hold faculty positions and have trainees of their own.

As my readers are well aware, I regularly attend professional meetings around the world – none match the excitement and intensity of COSM.

I look forward to another succesful meeting as we continue to build the next generation of Canadian obesity researchers, health professionals and policy makers.

You can follow live tweets from this meeting at #COSM2014

Waterloo, Ontario

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Friday, May 9, 2014

Obesity Is Highly Heritable – But Exactly How This Works Remains Mysterious

sharma-obesity-dna_molecule9One of the most fascinating aspects of obesity is that it is virtually as heritable as body height.

Yet, the hunt for the genes that determine body weight has been slow and we are probably not all that much closer to fully understanding exactly how genes influence body weight, than we were 20 years ago, when I myself was dabbling in genetic studies of complex diseases.

An article by the science writer Cassandra Willyard from Madison, Wisconsin, published in the Nature Outlook Supplement on Obesity does a valiant job of explaining where we currently stand in our understanding of the genetics of obesity.

The article discusses the contribution of genome-wide association studies (GWAS), which have linked about 75 genetic variants have to obesity.

“But GWAS studies aren’t perfect. They can lead researchers to important parts of the genome, but it can be difficult to sort out which gene within that region might be the culprit.”

Indeed, it appears that the conventional notion that much of the heritability of obesity would be explained by common genetic variants may be wrong.

Another possibility could well be that current GWAS studies don’t gene-environment interactions into account. Genes that influence body weight only under certain conditions, cannot be identified in the current studies as environmental exposure of individuals has not been well characterized in these studies.

“To resolve the issue, more than a hundred researchers launched a meta-analysis that included 45 studies involving more than 218,000 adults and 19,000 children. Not surprisingly, they found that people who carry the susceptibility gene had a higher risk of obesity. However, the researchers also observed that the risk appears to be reduced in people who are physically active.”

Another possibility may well be that obesity is not determined by common variants but rather by a large number of rare variants in the population (present in less than 5% of individuals, i.e. below the threshold of GWAS analyses).

The article also describes the additional complexity added by the recent work on epigenetics which, of e.g.

…”suggest that what happens in the womb can cause lasting changes in gene expression and influence disease risk even in adulthood, a concept known as fetal programming. This raises the possibility that a mother’s experiences during pregnancy — such as malnutrition — can influence the next generation.”

“The epigenetics of obesity isn’t only about the mother — the father’s experiences can have an impact too. When researchers in Australia fed male rats a fatty diet, the rats — as expected — put on weight and developed signs of diabetes. But, surprisingly, the weight gain also seemed to affect the rats’ daughters: the female offspring had trouble controlling their insulin levels despite being on a normal diet. And a study published in 2013 showed that children with obese fathers had less methylation on a particular region of the IGF2 gene than children who were born to lean fathers.”

As Wollyard explains,

“To show that an epigenetic change is due to inheritance, however, researchers have to look at multiple generations. When a pregnant woman experiences malnutrition or some other environmental stress, three are directly exposed…So, if a woman’s great grandchildren show a particular epigenetic change that is linked to environmental stress during their great grandmother’s pregnancy, that change can be said to be inherited rather than being a programming effect.”

But exactly what role transgenerational transmission of “acquired” genetic changes play in obesity remains unclear. Nevertheless, there is the distinct possibility that this type of inheritance may explain some of the missing heritability.

All we can say, is that there is a considerable likelihood that our genes may well have changed.

Toronto, ON

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Wednesday, March 26, 2014

How The FTO Gene Affects Body Weight

sharma-obesity-dna_molecule9Body weight is one of the most heritable of physiological traits – in fact (believe it or not), it is just as heritable as body height.

Among the many genes associated with body weight, data for the FTO gene have been most consistent.

But these finding have puzzled researchers, as genetic manipulations of the coding regions of the FTO gene have large effects on body weight, without any apparent change in the function of this gene.

Now, a paper by Scott Smemo and colleagues, published in NATURE, suggests a mechanism for how variants of the FTO gene may affect body composition.

The answer lies in the way that the region of the FTO gene associated with obesity directly interacts with another gene IRX3, located a few megabases away on the same chromosome. This interaction appears conserved across species all the way back to the zebrafish.

Consistent with this finding, it turns out that the obesity-associated single nucleotide polymorphisms of the FTO gene are associated with changes in the expression of IRX3, but not FTO, in human brains.

Also consistent with this idea is the fact that IRX3-deficient mice have a 30% lower body weight, primarily due to less fat mass and an increase in basal metabolic rate with browning of white adipose tissue. The animals also appear resistant to the effects of a high-fat diet and appear protected against diabetes.

Furthermore, expression of a dominant-negative form of IRX3 in the hypothalamus reproduces the metabolic phenotypes of Irx3-deficient mice.

Thus, these findings suggest that FTO exerts its effect on body weight through its functional impact on the IRX3 gene, a gene that has so far not been linked to body weight regulation.

This is of particular significance, as IRX3 appears to be a “master gene” that controls the expression of other genes in many tissues including the brain and fat cells.

Given that variants of the FTO gene are frequent in the population and consistently linked to obesity (and type 2 diabetes), these findings may take us one step closer to a molecular target for anti-obesity interventions.

Edmonton, AB
ResearchBlogging.orgSmemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, & Nóbrega MA (2014). Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature, 507 (7492), 371-5 PMID: 24646999

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Friday, March 7, 2014

Leipzig Forging Its Way As Leaders in Obesity Research

Seal Faculty of Medicine, University of Leipzig, GermanyThis week, for the 5th consecutive year, I have had the privilege of participating in an extensive review of the obesity research program at the University of Leipzig.

I believe that it is fair to say, that starting from scratch, this centre has certainly shown a most remarkable growth and advancement in both fundamental and clinical aspects of obesity research.

It is indeed an honour to have had the opportunity to help evaluate and guide this world-class research program over the past five years.

It is particularly heartwarming to see how much emphasis this program has placed on supporting the career development of the next generation of obesity researchers in Germany.

As the program goes into the renewal phase for hopefully acquiring funding for the next five years, here is a link to past posts on their achievements.

Leipzig, Germany

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In The News

Diabetics in most need of bariatric surgery, university study finds

Oct. 18, 2013 – Ottawa Citizen: "Encouraging more men to consider bariatric surgery is also important, since it's the best treatment and can stop diabetic patients from needing insulin, said Dr. Arya Sharma, chair in obesity research and management at the University of Alberta." Read article

» More news articles...


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