Friday, December 5, 2014

Hypothalamic Inflammation In Human Obesity

sharma-obesity-astrogliosisRegular readers may recall the exciting body of work from animal models of obesity showing that hypothalamic inflammation involving microscarring (gliosis) may play an important role in appetite and energy regulation in obesity.

Now, a study by Josep Puig and colleagues from the University of Girona, Spain, published in the Journal of Clinical Endocrinology and Metabolism, provides evidence for a similar process in humans.

The researchers used an MRI technique called diffusion tensor imaging (DTI) to measure hypothalamic damage in 24 consecutive middle-aged obese subjects (average BMI 43) and 20 healthy volunteers (average BMI 24).

Not only did the obese participants show greater signs of hypothalamic inflammation but these changes were also strongly associated with higher BMI, fat mass, inflammatory markers, carotid-intima media thickness, and hepatic steatosis and lower scores on cognitive tests.

While these studies do not prove cause and effect, these findings are consistent with findings in animal models and point to the role of pro-inflammatory pathways in the areas of the brain known to be intimately linked to appetite and energy regulation.

Understanding what exactly triggers this inflammatory response (in animal models, one fact appears to be a high-fat diet) and how this process could be inhibited, may open new avenues for obesity prevention and treatment.

@DrSharma
Madrid, Spain

ResearchBlogging.orgPuig J, Blasco G, Daunis-I-Estadella J, Molina X, Xifra G, Ricart W, Pedraza S, Fernández-Aranda F, & Fernández-Real JM (2014). Hypothalamic damage is associated with inflammatory markers and worse cognitive performance in obese subjects. The Journal of clinical endocrinology and metabolism PMID: 25423565

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Wednesday, December 3, 2014

Does Your Liver Control Your Appetite?

Fatty Liver

Fatty Liver

The answer may well be “yes”, at least if you happen to be a mouse.

In a rather exciting study by Iliana López-Soldado and colleagues from the Institute for Research in Biomedicine, Barcelona, published in DIABETES, the researchers show that increased liver glycogen content may affect appetite (measured as food intake) and otherwise have beneficial effects on metabolism.

In their experiments, the researchers used genetically modified mice, which overexpress an enzyme (PTG) resulting in increased liver glycogen.

Not only did these animals reduce their food intake when fed a high fat diet, they also did not develop the typical glucose intolerance, elevated insulin levels and fatty liver seen in normal mice on this diet.

Apart from losing weight (associated with lower leptin levels), these animals also had lower expression of neuropeptide Y (NPY) and higher expression of propiomelanocortin (POMC) in the hypothalamus.

Thus, the authors summarize their findings as follows:

:…liver glycogen accumulation caused a reduced food intake, protected against the deleterious effects of a HFD and diminished the metabolic impact of fasting. Therefore, we propose that hepatic glycogen content be considered a potential target for the pharmacological manipulation of diabetes and obesity.”

As a number of compounds exist that may do exactly that, these studies may point to a novel pathway for the pharmacological treatment of obesity – but let’s keep in mind that the road from finding in mice to effective treatments in humans is a long and thorny road.

@DrSharma
Edmonton, AB

ResearchBlogging.orgLópez-Soldado I, Zafra D, Duran J, Adrover A, Calbó J, & Guinovart JJ (2014). Liver glycogen reduces food intake and attenuates obesity in a high-fat diet-fed mouse model. Diabetes PMID: 25277398

 

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Friday, November 28, 2014

When Something is Not Better Than Nothing

diet journalThis is the title of a recent article by Nikhil Dhurandar and other members of the Energy Balance Measurement Working Group (of which I am a member), published in the International Journal of Obesity and refers to the inadequacies of our current methods for assessing energy intake and expenditure.

In the paper, the authors argue that while an assessment of energy balance may well be a critical issue both for research and clinical practice, our current methods for assessing this are woefully inaccurate and may well be leading us in the wrong direction.

Thus, for example, there is no shortage of information on the fact that self-reported dietary energy intake (EI) is woefully inaccurate (despite all efforts over the past decades to try and make this more accurate) to the point of being near useless in individuals and even less meaningful in population studies – at least when it comes to the assessment of energy balance.

The same is unfortunately true for assessments of physical activity energy expenditure (PAEE) where errors ranging in the 100s of calories are the norm rather than the exception.

This leads the authors to the rather sweeping conclusion that,

“…self-reports of EI and PAEE are so poor that they are wholly unacceptable for scientific research on EI and PAEE. While new strategies for objectively determining energy balance are in their infancy, it is unacceptable to use decidedly inaccurate instruments, which may misguide health care policies, future research, and clinical judgment. The scientific and medical communities should discontinue reliance on self-reported EI and PAEE.”

While this may well hold true for research, I am not that sure about the implications for clinical practice.

This is because, the very act of self-monitoring has been shown to influence behaviour – irrespective of the precision of such monitoring (at least I am not aware of a single study showing that the accuracy of food records makes any difference to the outcome).

There is indeed overwhelming evidence that patients who use any form of self-monitoring (pen and paper or electronic) eat better and are more physically active than people who don’t.

While trying to determine someone’s precise energy balance by poring over these records is a rather futile exercise (the difference between the records and what actually happens may be in the 100s of calories), I do know that my patients who keep food and activity records do better than those who don’t.

Nevertheless, as far as research is concerned (or making clinical decisions based on assuming that the actual energy balance is anywhere close to the deceptively precise numbers calculated from such record), I agree with the authors that our current methods are highly inadequate and, what is worse, may well be misleading.

I, for one,happily ignore most of the data that comes from self-reported studies on diet or activity (which, incidentally is the vast majority of research on these issues), never mind that much of these data come from epidemiological studies, where any inference of causality is speculation at best.

On the other hand, precise or not, I do encourage all of my patients to self-monitor as I know this changes behaviour – no matter if these records are off by 100s of calories.

@DrSharma
Barcelona, Spain

ResearchBlogging.orgDhurandhar NV, Schoeller D, Brown AW, Heymsfield SB, Thomas D, Sørensen TI, Speakman JR, Jeansonne M, & Allison DB (2014). Energy balance measurement: when something is not better than nothing. International journal of obesity (2005) PMID: 25394308

 

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Thursday, November 27, 2014

Would You Like Some Guilt With That Popcorn?

popcornYesterday, I blogged about the McKinsey discussion paper that calls on governments to throw everything they’ve got at the obesity epidemic – proven or unproven – anything is better than nothing.

That said, it is indeed timely that this week, the US-FDA announced sweeping regulations on putting calories on menus, not just in fastfood restaurants but also in grocery stores, vending machines, and movie theatres.

Personally, I am all for it – never mind that we have yet to show that providing this information at the point of purchase actually changes behaviour of the target population (namely the people who do need to watch their calories) – I, for one, do find this information helpful.

Thus, every time I visit a McDonalds restaurant (yes, I do), I study the nutritional information that this restaurant chain has been making available to any customer who bothers to ask for decades.

Indeed, I do admit to deriving a kind of voyeuristic pleasure in seeing those astonishingly high numbers on certain food items and cannot help myself from inwardly shaking my head at the poor schmucks who order those foods.

What I do wonder, however, is whether knowing these numbers has ever actually changed my own behaviour.

Take movie popcorn for instance – I love it! (interestingly this is a habit that I only developed since moving to Canada).

Not that I am not aware that a large popcorn can easily have all the calories I need for the rest of the weekend – yup, I know that – indeed, I am making an “informed choice”.

In the few milliseconds I spend thinking about whether or not I may wish to skip the popcorn this time, those calorie numbers do regularly flash through my mind – in the end, the popcorn always wins.

So how will having the numbers up on the menu board staring in my face change things for me?

My guess is that I’ll still buy the popcorn, except now it will come with an even larger portion of guilt than before.

Obviously, with the numbers up there for everyone to see (including the people in line behind me), there may well now be an added tinge of embarrassment on top of the guilt.

Well, I may not be the typical consumer or even the target of these measures – after all these are meant for the people who could obviously do with some nudging towards eating a healthier diet (not really sure why I am excluding myself from this list).

Yet, I don’t mind these measures, I have always considered this a good idea.

But will having these numbers staring me in the face everytime I eat out change my consumption of popcorn? Probably not.

Will they make me think thrice (I already think twice)? Perhaps.

So to sum up, funnily enough, I find myself in full support of this measure – even if I am not really sure why.

I guess anything is better than nothing.

@DrSharma
Frankfurt, Germany

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Friday, November 14, 2014

Video: Principles of Obesity Management

Arya Sharma Kingston Nov 2014Over the past weeks, I have given a rather large number of talks on obesity management to a variety of health professionals. Now, there is a recording of one of my talks (which I gave a few days ago in Kingston, Ontario) on Youtube.

Although the quality of the recording is perhaps not the best and the talk is rather long (about 100 minutes), for those of you, who would like to have a better grasp of how I think about and approach obesity management, here is the link.

Feedback is very much appreciated.

@DrSharma
Edmonton, AB

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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

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