Notes From The Obesity Society Conference 2010

Last month the Obesity Society held its 28th Annual Scientific Meeting, Obesity 2010, in San Diego. A number of prominent researchers, physicians, advocates, and business leaders in the rapidly growing field of obesity research came to discuss and present their recent work and insight into the nature of the global obesity epidemic.

Why was ASweetLife there, and interested? Well, as most of you know, the obesity epidemic, with over a third of America labeled overweight and the rest of the world falling into step, is closely tied to the diabetes epidemic. Excess body weight is associated with numerous adverse health complications, including heart disease, cancer, Alzheimer’s, and, of course, type 2 diabetes.

So, when the Obesity Society met to discuss the causes, complications, and solutions to the problem of obesity, ASweetLife was there, listening in. Some notes from the field:

Causes: Programmed for Obesity

No one denies the behavioral underpinnings of obesity. (As the common quip puts it, the most effective diet is “Eat less, exercise more.”) However, increasingly researchers find that behavior is not the whole story, and that individuals– both human and lab-mouse– can have a predisposition towards obesity. This can take the form of a propensity for overeating, a more sedentary disposition, an over- or under-abundance of certain molecular components of the metabolic pathway, and any number of other mechanisms actively being explored.

One particularly interesting analysis of what programs people for obesity came from Mary Elizabeth Patti of the Joslin Diabetes Center. She presented research into the role of the prenatal and early post-natal environment in defining a person’s relative risk of being overweight later in life. Even outside of the field of obesity, studies have established that maternal stressors, including under- or over-nutrition, an excess of stress hormones, and insufficient oxygen levels in the placenta, can have lasting effects on the tissues and biological tendencies of offspring. For Patti, this prenatal predisposing raises the particular question– what in the maternal milieu makes a person more likely to develop type 2 diabetes, and what can we do about it?

One element of the prenatal environment that Patti finds especially correlated with the risk of type 2 diabetes is birth weight; babies with either a high birth weight or a low birth weight as compared to other infants are more likely to suffer from metabolic syndrome later in life. Notably, this correlation does not imply that low or high birth weights cause obesity or diabetes. Rather, birth weights outside of a certain range might be biomarkers– measurable biological indicators– that can alert physicians and researchers to other underlying problems.

This association of low birth weight, caused often by maternal under-nutrition, with adverse health effects for the offspring later in life, is not new. The relationship between maternal under-nutrition and offspring health was discussed widely in the nineties in the context of  long-term studies conducted on the children of mothers pregnant during the World War II era famine in the Netherlands, the Dutch Hunger Winter. Contrary to expectations, researchers found that the low birth weight children of mothers who underwent malnutrition during pregnancy were much more likely to suffer from obesity, heart disease, and glucose intolerance.

Patti attributes this counterintuitive correlation between low birth weight and later metabolic syndrome in part to altered tissue development and basal hormone levels in utero. Looking at mice whose mothers experienced caloric and nutritional restriction for one week during gestation, Patti saw an average 15% drop in birth weight, followed by a period shortly after birth in which the offspring mice catch up to their normal-sized peers. Even after reaching a normal weight, though, the low birth weight mice showed evidence of excess fat in the abdomen, disregulation of insulin secretion, abnormal patterns of insulin clearance in the liver, and insulin resistance. Further, the mice had lower muscle mass than their peers, with fewer muscle stem cells and a reduction in markers of muscle regeneration, and larger adipocytes, which are the primary fat-storage cells in the body.

Another part of the story, Patti theorizes, is the particular period after birth during which the mice eat in excess to make up for their low birth weight and reach normal weight. This period, which Patti terms “catch-up growth,” is marked by a point at which an individual’s height percentile as compared to his peers crosses that of his weight percentile, indicating that he has adjusted his weight to be more in line with what would be expected with height (or in the case of mice, length). Patti found that mice who experienced a stage of catch-up growth were especially at risk for abnormal metabolic profiles and insulin resistance. However, if the growth of low birth weight mice was restricted during the post-natal period, and mice were prevented from quickly catching up with their peers, glucose tolerance and metabolic profiles were normalized.

What does this all mean for humans, though? Given the correlation seen commonly between low birth weight and adverse health outcomes later in life, Patti suggested that a closer look at the post-natal catch-up period was warranted. There are, of course, risks to limiting a child’s ability to quickly raise his weight after birth; catch-up growth and reaching a normal weight profile is associated with increased immune function and greater height later in life. However, the degree and rate of catch-up growth perhaps needs to be closely watched and modulated, in order to ensure that for humans and mice, the individual does not establish a metabolic pattern early on that could predispose him to obesity, diabetes, and heart disease later in life.

Complications: An Inflammatory Infiltration

This triumvirate of obesity, diabetes, and heart disease was a common one at the conference. The Obesity Society notes that “obesity is a leading cause of United States mortality, morbidity, disability, healthcare utilization and healthcare costs,” largely because of the numerous diseases that coincide with obesity. Not surprisingly, therefore, many sessions during the conference were dedicated to understanding the mechanisms that underlie the complications associated with diabetes, from the chemical imbalance that accelerates certain cancers to the plethora of circulating fatty acids that desensitize tissues to insulin.

There are big open questions in this area especially around the nature of the immune system reaction to obesity. Nearly a decade ago, there was a revolution in the field as people began to realize that part of the pathology of obesity was that adipose tissue– that is, fat tissue– is composed of heterogeneous types of cells, including not just adipocytes but also numerous cells active in the immune system. These cells, it was found, were recruited to fat tissue in the abdomen as a person became obese, and this in turn had drastic effects on the nature and types of intercellular signaling that occurred within the body.

Since the initial discovery of the immune system changes caused by obesity, much research has been done to elucidate the scope and mechanisms of the interplay of the immune system and fat. Many scientists spoke about their research into the role of obesity-driven immune changes in a wide array of diseases, including cancer, cardiac failure, and diabetes.

One avenue of increasing interest was addressed by Alyssa Hasty of Vanderbilt University. Hasty and her team have been investigating the role of a particular receptor for immune system signals, Toll-Like Receptor 4 (TLR4), in inflammation and free fatty-acid management. The TLR4 receptors exist in the innate immune cells within the body, including those found in adipose tissue, and they bind to circulating saturated fatty acids. Once they bind, the receptors initiate a cascade of immune signals that contribute to inflammation of the surrounding environment.

Because TLR4 specifically reacts to saturated fatty acids, and in fact can be blocked by poly-unsaturated fatty acids (like the Omega-3 fatty acids), it is a compelling potential link in the relationship between obesity and inflammation. In order to determine the exact role of these receptors, Hasty looked at mice who lacked the ability to express TLR4 at all; without TLR4, she asked, how would mice respond to diets high in saturated fat? Would there be a reduction in inflammation as compared to normal mice, and would this be beneficial for the insulin sensitivity of the mice?

After a series of experiments with the TLR4-deficient mice, Hasty and her team found that, well, it’s complicated. They hoped to see an overall reduction in inflammation and therefore an improvement in insulin sensitivity. Instead, they saw that the TLR4-deficient mice were less fat overall, but only for the set of mice fed the diet high in saturated fat; mice fed a normal diet or one high in unsaturated fats were no better than the control mice with comparable diets. Further, the lack of TLR4 did not result in fewer immune cells infiltrating the adipose tissue, and it did not have an effect on the overall glucose tolerance of the mice.

Despite the lack of big, startling wins, Hasty did find some very interesting and promising tendencies in the mice without TLR4. They may have had similar numbers of immune cells residing in fat tissue, but the type of cell was slightly different; instead of mostly being the pro-inflammatory type, the cells skewed more towards the type that is responsible for wound-repair and post-inflammation cleanup. Perhaps as a result, the adipose tissue itself– though as noted above, not the whole body– was more insulin sensitive.

Hasty’s results, neither ideal nor clear, indicate the need for further investigation and research into how TLR4 interacts with free fatty acids, but carry an important message nonetheless: the complexity of the interactions between the immune system and obesity go beyond even just the innate immune system, and show how crucial it is to gain a better understanding of obesity before too many more people suffer from the associated disorders.

Solutions You Can Pay For:

Regardless of how interesting and promising it may be, inconclusive research doesn’t have an answer for people when they want it: now now now. For that, I had to turn to an alternate area of the Obesity Conference: the showroom floor! There’s nothing like glossy marketing material to reassure me that It Will All Be Okay.

And the Obesity Conference showroom floor did not disappoint. It was strangely bimodal as compared to other marketing rooms I’ve seen; half of the booths were strictly research-targeted, with displays of the newest chemical reagents or plastic apartment complexes designed for the housing and feeding of mice, and the other half of the booths were aimed towards clinicians who themselves were responsible for the housing and feeding of patients.

Some of my favorites:

* Control Appetite Management Snacks: Dr. Francine Kaufman, the high-profile endocrinologist who wrote Diabesity and who treats Nick Jonas, is featured prominently on all the marketing material for these snacks designed to be good for weight-loss and blood sugar control. In theory, the extremely slow digestion of the carbohydrates in these snacks keeps hunger at bay longer and mitigates post-meal spikes. The secret? Uncooked cornstarch, an extremely complex carbohydrate, which Kaufman found in trials to be effective in both glucose control and weight management. I don’t know if it works, but the samples tasted good enough to be worth trying if you struggle with the rate of carbohydrate digestion.

* ActiGraph activity monitoring systems: ActiGraph makes several devices designed to measure and monitor activity levels throughout the day. The products, which vary slightly depending on whether they are designed for clinical or consumer use, can measure ambient light levels (to record time spent sleeping), heart-rate, and direction and force of motion. The data stored on the compact devices can then be uploaded to a computer for review, analysis, and fine-tuning. According to the sales personnel, the ActiGraph monitors are designed both for ensuring patients meet discussed requirements and for optimizing normal activity levels throughout the day. Unfortunately, there is no mobile interface yet or real-time data access. My personal interest in these devices was very particular though– I’m less concerned about general activity levels, but the cheaper and more ubiquitous activity-monitoring devices, with gyroscopes or GPS, become, the more likely I am to see one in an auto-adjusting insulin pump sometime soon!

* Tanita Total Body Composition Analyzers: Ever wanted to know the percentage of your left leg that is fat? Well, regardless of your answer, Tanita products help you do just that. Tanita makes a series of scales for consumer or clinical use. The scales measure not just weight, but also your body’s level of resistance to electrical currents passed through tissue. Based on the fact that different types of tissue have different levels of resistance, the scales can then predict fat percentage and muscle mass across different parts of the body. And, in what strikes me as a rather humorous, sci-fi worthy process, the clinical versions print up receipts, complete with your weight, Body Mass Index, and fat percentages by body part. Such tools can be useful for athletes fine-tuning muscle mass, and also for doctors attempting to help patients reduce fat levels, especially in the abdominal area. (And what’s my readout? Hey now, didn’t your mother ever tell you not to ask a woman about her weight?)

All in all, then, the message at the Obesity Conference was clear– obesity is an overwhelming epidemic in the US, and if we don’t act to better understand and address it, more and more people will suffer from the consequences, including immune disregulation, heart disease, and of course diabetes. What, as a nation, are we doing about it?

Karmel Allison is science editor of ASweetLife.  She writes the blog Where is My Robot Pancreas?.

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