Friday, August 8, 2014

Healthy Obesity: More Questions Than Answers?

sharma-obesity-visceral-fat-mriRegular readers will be well aware of the evidence that a subset of people living with obesity can be remarkably healthy despite carrying a rather large amount of body fat.

This issue of “healthy obesity” was the topic of the 13th Stock Conference of the International Association of the Study of Obesity, the proceeding of which are now published in Obesity Reviews.

As the authors note,

“The ‘healthy obese’ phenotype was described in the 1980s, but major advancements in its characterization were only made in the past five years. During this time, several new mechanisms that may be involved in health preservation in obesity were proposed through the use of transgenic animal models, use of sophisticated imaging techniques and in vivo measurements of insulin sensitivity. However, the main obstacle in advancing our understanding of the metabolically healthy obese phenotype and its related long-term health risks is the lack of a standardized definition.”

The latter is a real problem because finding people with obesity, who are truly metabolically and otherwise healthy becomes harder the higher the BMI gets – this makes the study of this phenomenon rather challenging.

Nevertheless,

“One of the most consistent characteristics of metabolic health in obesity across studies in humans is reduced liver lipid. This is likely the consequence of increased capacity for storing fat coupled with improved mitochondrial function in adipose tissue and decreased de novo lipogenesis in liver. This can also result in decreased deposition of lipids, including bioactive species, in skeletal muscle. Decreased adipose tissue inflammation with decreased macrophages and a unique T-cell signature with an anti-inflammatory circulating milieu were also suggested to characterize metabolic health in obesity. Anecdotal data support a possible role for healthier lifestyle, including increased level of physical activity and healthier diet. It remains to be established whether a favourable metagenomic signature is a characteristic of metabolic health in obesity.”

Finland’s, Dr Kirsi Pietiläinen explained that,

“..three energy dissipation pathways, oxidative phosphorylation, fat oxidation and amino acid catabolism showed preserved pathway activities in subjects who are MHO at a level similar to their lean counterparts. In contrast, these pathways were significantly down-regulated in adipose samples from obese twins with metabolic disturbances. Another potential hallmark of metabolic health, a favourable inflammatory profile of the adipose tissue was also observed in the MHO twins. Also, the fat cells of the MHO twins were smaller with evidence of more active differentiation processes within the fat tissue. As multiple mitochondrial pathways are vital in adipocyte differentiation [29], it is possible that mitochondrial malfunction impairs the development of new fat cells, which in turn results in an inability of the adipose tissue to expand under conditions of energy excess. This failure of fat cell proliferation has long been suspected to constitute the framework for ectopic fat storage, insulin resistance and type 2 diabetes.”

Other speakers discussed other aspects including immune function and microbiata in this phenomenon.

Finally, the authors concluded that,

“identifying underlying factors and mechanisms associated with this phenotype will eventually be invaluable in helping the scientific and medical community understand factors that predispose, delay or protect obese individuals from metabolic disturbances. It is essential to underscore that the MHO concept presently only address the cardio-metabolic risks associated with obesity; it is therefore important that patients who are MHO are still very likely to present many other obesity-related complications such as altered physical and/or physiological functional status, sleep problems, articulation and postural problems, stigma, etc. Importantly, the MHO concept supports the fact that classification based on excess adiposity per se (e.g. BMI or body composition if available) should be supplemented with obesity-related comorbidities, e.g. with fasting insulin as proposed by the Edmonton obesity classification system.”

Certainly a space to watch as we learn more and more about the “healthy obesity” phenotype.

@DrSharma
Edmonton, AB

ResearchBlogging.orgSamocha-Bonet D, Dixit VD, Kahn CR, Leibel RL, Lin X, Nieuwdorp M, Pietiläinen KH, Rabasa-Lhoret R, Roden M, Scherer PE, Klein S, & Ravussin E (2014). Metabolically healthy and unhealthy obese – the 2013 Stock Conference report. Obesity reviews : an official journal of the International Association for the Study of Obesity PMID: 25059108

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Thursday, July 31, 2014

Low Adipocyte Formation Is Associated With Abdominal Obesity

sharma-obesity-adipocytes3One of the key concepts about the deposition of visceral and ectopic fat is the inability of “healthy” subcutaneous to readily expand to accommodate excess calories. This is why people with large fat cells and those with less or no subcutaneous fat (as in partial or complete lipodystrophy) display features of the metabolic syndrome.

In line with these observations, a study by Andre Tchernof and colleagues from the University of Laval, Quebec, in a paper published in ADIPOCYTE show that low adipogenic capacity of subcutaneous adipose tissue is associated with visceral obesity, visceral adipocyte hypertrophy, and a dysmetabolic state.

The researchers studied adipocytes and preadipocytes isolated from subcutaneous and visceral fat samples from 35 women undergoing gynecological surgery and assessed body fat distribution by CT as well as fasting plasma lipids and glycemia.

Using an in vitro differentiation assay, they found that lower adipogenic rates were strongly associated with increased visceral cell size and dyslipidemia.

In addition, When matched for BMI, women with low subcutaneous preadipocyte adipogenic rates had a higher visceral adipose tissue area, omental adipocyte hypertrophy, higher VLDL-lipid content and higher fasting glycemia.

All of these findings are in line with the notion that low subcutaneous preadipocyte differentiation capacity in vitro is associated with visceral obesity, visceral adipocyte hypertrophy, and a dysmetabolic state.

Once again, as regular readers should be aware, not all fat is equal.

@DrSharma
Edmonton, AB

ResearchBlogging.orgLessard J, Laforest S, Pelletier M, Leboeuf M, Blackburn L, & Tchernof A (2014). Low abdominal subcutaneous preadipocyte adipogenesis is associated with visceral obesity, visceral adipocyte hypertrophy, and a dysmetabolic state. Adipocyte, 3 (3), 197-205 PMID: 25068086

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Tuesday, July 8, 2014

Does BMI Underestimate Adiposity in Kids?

sharma-obesity-kids-scale2Regular readers are well aware of my reservations regarding the use of BMI as a diagnostic parameter in clinical practice. After all, while BMI may tell us how big someone is, it certainly is not a good measure of how sick someone is.

But to be honest, BMI was never intended as a measure of disease – it was (at best) introduced as a surrogate measure of adiposity (fatness).

Nevertheless, supporters of BMI continue to argue that it is still a good measure of fatness and as such should remain part of standard assessment – even in kids.

Now, a paper by Javed and colleagues, published in Pediatric Obesity, examines how well BMI performs as a means to identify obesity as defined by body fatness in children and adolescents.

The authors conducted a systematic review and meta-analysis of 37 studies in over 53,000 participants assessing the diagnostic performance of BMI to detect adiposity in children up to 18 years.

While the commonly used BMI cut-offs for obesity showed showed a high specificity (0.93) to detect high adiposity, the sensitivity was much lower (0.73) – particularly in boys.

This means that kids who exceed the current BMI cut-offs are indeed very likely to have fatter bodies (for what it’s worth).

On the other hand, relying on BMI cut-offs alone will miss as many as 25% of kids whose body fat percentage exceeds current definitions of adiposity.

Thus, assuming that bod fatness or adiposity is indeed a clinically useful measure of health, the use of BMI alone will ‘underdiagnose’ adiposity in a significant proportion of kids (especially boys) who may well be at risk from excess fat.

A word of caution about fatness is certainly in order – as in adults, much depends on exactly where the fat is located (abdominal or ectopic vs. subcutaneous) and other factors (e.g. cell size, inflammation, insulin sensitivity, etc.).

Thus, even if BMI was a perfect measure of body fat, it would probably still require further examinations and tests to determine exactly whether or not this “extra” fat poses a health risk.

As in adults, a clinical staging system similar to the Edmonton Obesity Staging System may be a fat better indicator of determining which kids may need to worry about their body fat and which don’t.

@DrSharma
Edmonton, AB

Hat tip to Kristi Adamo for pointing me to this study

ResearchBlogging.orgJaved A, Jumean M, Murad MH, Okorodudu D, Kumar S, Somers VK, Sochor O, & Lopez-Jimenez F (2014). Diagnostic performance of body mass index to identify obesity as defined by body adiposity in children and adolescents: a systematic review and meta-analysis. Pediatric obesity PMID: 24961794

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Tuesday, June 24, 2014

Time To Go Nuts About Nuts?

sharma-obesity-nutsNuts are reportedly chock full of all kinds of nutrients and are probably among the healthiest of snacks. However, they are also among the most calorie-dense foods – a small handful of nuts (~30 g) can easily add up to 150-200 cals.

So, do high consumers of nuts run the risk of weight gain?

This issue is discussed in depth by Sze Yen Tan and colleagues in a paper published in the American Journal of Clinical Nutrition, in which they review the effects of nuts on appetite, food intake, metabolism, and body weight.

While eating nuts may not exactly lead to weight loss, most studies find that consumption of “extra” calories as nuts leads to substantially less weight gain than may be expected based on their caloric content.

Their review reflect a number of ways in which nuts may have this effect:

Effect on hunger and appetite:

“…nut ingestion suppresses hunger and desire to eat and promotes fullness. These sensations may aid dietary compensation that offsets much of the energy contributed by nuts. However, strong compensation can also occur independently of reported appetitive effects. This may reflect imprecision in appetite measurement or a truly independent uncharacterized mechanism.”

Mastication (chewing):

“Nuts require considerable oral processing effort and this may, in part, account for the often-noted less-than-predicted effect of their consumption on body weight. The mechanical act of chewing reportedly generates satiation signals through cognitive, neural, endocrine, and physical (eg, gastric emptying) mechanisms; augments cephalic phase responses linked to appetite; influences digestion efficiency; modestly increases energy expenditure; and elicits dietary compensation.”

Nutrient absorption:

“A number of studies have evaluated the efficiency of energy absorption from ground and tree nuts through feeding trials. All showed substantive increases in fecal fat loss with nut consumption, although the values ranged widely from ∼5% to >20%”

Energy expenditure:

“Collectively, there is some evidence that nut consumption increases thermogenesis, but the data are not robust and there is no clear mechanism. One possibility is that the lipid from nuts is absorbed over a prolonged period of time, leading to a small but sustained source of substrate that fuels thermogenesis and could appear as an increase in REE.”

Fat metabolism:

“It has been proposed that nut consumption elevates fat oxidation and preferentially reduces body fat mass, especially in the viscera. These actions are attributed to their high unsaturated fat content….Human studies incorporating different nuts into the diet at realistic doses are needed to determine the effect of nut consumption on body composition.”

With regard to impact on body weight, the authors reach the following conclusions:

Adding nuts to habitual diets:

“Although there are reports of small, but significant increases in body weight with nut consumption, the preponderance of evidence indicates that under controlled or free-living situations, nut consumption does not promote weight gain.”

Eating nuts in calorie-restricted diets:

“The inclusion of nuts in energy-restriction regimens does not impede weight loss. In several trials in which nuts did not augment weight loss, there was a reduction in cardiovascular disease risk indexes in the nut-consuming groups, suggesting that such benefits derive from properties of the nuts rather than just weight change.”

Eating nuts in weight maintenance:

“Several studies assessing the role of nut consumption in weight-maintenance programs have noted a decrease in body weight from baseline. Whether this is due to a greater thermic effect of food or REE effect of the nuts compared with the foods they displaced in the diet has not been established. Nevertheless, current data indicate that the inclusion of nuts in a weight-maintenance program will not lead to weight gain and may aid weight loss.”

Thus, in summary, the authors conclude that,

“…evidence indicates that they pose little challenge to and may even aid weight management. This is attributable to the strong dietary compensation effects they elicit, inefficiency in the absorption of the energy they provide, and possibly an elevation of energy expenditure and fat oxidation.”

As a general caveat to all of these data, it needs to be noted that results varied widely depending on the types of nuts and how exactly these nuts were consumed (e.g. as snacks or added to meals – the former often being more favourable than the latter).

Also, many of the studies had relatively small number of participants and were of rather short duration.

Nevertheless, it does appear that going nuts about nuts may not be quite as detrimental to your weight as their energy content would suggest.

@DrSharma
Toronto, ON

ResearchBlogging.orgTan SY, Dhillon J, & Mattes RD (2014). A review of the effects of nuts on appetite, food intake, metabolism, and body weight. The American journal of clinical nutrition, 100 (Supplement 1) PMID: 24920033

 

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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

@DrSharma
Waterloo, Ontario

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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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