I'll Take Catch-Up With Those Fries

Yesterday, I attended the "Crosstalk" symposium at ECO 2008 here in Geneva.

Once again, I was fascinated by Abdul Dulloo's (Co-Chair of the Symposium) talk on the phenomenon of "catch-up" fat.

Simply stated, this phenomenon describes the preferential accumulation of fat tissue as part of any weight-gain process that follows an energy deprived state (See Dulloo's excellent 2008 review for more on this topic).

Interestingly, this phenomenon occurs irrespective of whether the energy-deprived state is caused by voluntary or enforced starvation, dieting, anorexia or severe illness including sepsis or cancer.

In fact, it even occurs in small-for-gestational-age babies, who manage to rapidly make up for their low birth weight by rapidly tucking away those calories in those chubby fat depots.

Even more interestingly, data suggest that the excess calories that are tucked away are only partly derived from increased caloric intake. Most of them come from preferential partitioning of energy to the fat stores, largely by dramatically turning down skeletal muscle thermogenesis.

This means than even if you are careful not to "overfeed", your lean tissue will happily deprive itself for the benefit of those fat depots.

In animal experiments, high-fat refeeding appears to make this phenomenon even more pronounced.

All of this appears to be related to substantial insulin resistance that occurs during this "regain" phase and researchers are still trying to figure out what exactly makes the muscle "slow down" in order for the fat to accumulate.

Teleologically all of this makes sense. The idea perhaps is to rapidly take up those calories (following the famine or illness) and store them away - let's worry about rebuilding the lean mass later.

Unfortunately, at least in animals, this process may be detrimental in the long term. There is now a fairly consistent body of evidence that shows "catch-up" growth to be a risk factor for the development of cardiometabolic risk factors including abdominal obesity, type 2 diabetes, and dyslipidemia - all eventually leading to heart disease.

As regular readers may recall, I recently blogged about the apparent increased risk for the metabolic syndrome with weight cycling - perhaps a reflection of this phenomenon.

Whatever the causes and consequences of catch-up weight, the phenomenon is very real - people tend to get fatter with every diet; patients recovering from cancer tend to put on massive amounts of fat when they recover - most interesting indeed.

What if abdominal obesity is not a consequence of overeating alone but rather a result of past deprivation?

I guess I was not too far off the mark, when the New York Times recently quoted me as saying,"You might want to focus on being as healthy as you can and not obsess about your weight”.

Certainly no point losing weight if it just comes back as fat - i.e. unless you seriously believe you can keep it off by sticking to your weight management strategy for life!

AMS
Geneva, Switzerland

Does Surviving Cancer Lead to Weight Gain?

Yesterday's big news was the study by Kerry Courneya, professor and Canada Research Chair in Physical Activity and Cancer at the University of Alberta, published in CANCER.

I am not going to repeat the findings or the data here because this was nicely summarized by Sharon Kirkey from Canwest News Service in the Edmonton Journal.

The bottom line is that cancer survivors are apparently not exercising more or eating healthier than everyone else, and are therefore at least as, if not even more, likely to develop obesity than the average Canadian.

This is particularly true for survivors of breast and colon cancer, which are particularly likely to recur with lack of physical activity, unhealthy eating and weight gain.

The dramatic impact of weight on cancer risk is perhaps best demonstrated by the observation that obesity surgery, which on average reduces body weight by 25%, results in an almost 60% reduction in cancer mortality! (see Adams et al. for an example of such a study).

I guess it just goes to show that cancer survivors are no less susceptible to the consequences of our obesogenic environment, which certainly does not make weight control easy, even at the best of times.

That is of course, unless there is something special about surviving cancer that makes you more likely to gain weight - an interesting hypothesis pursued by other researchers here at the University of Alberta.

I can think of a number of reasons why surviving cancer could predispose to weight gain: "catch-up" fat, depression, "post-traumatic" stress, anxiety, susbtance abuse, "overfeeding", immobility, medications, and perhaps a few others.

Whatever the reasons, it looks like we may now need intervention programs to specifically address weight gain and obesity in cancer survivors?

For one, educating cancer survivors about the links between excess weight and cancer would be a start.

My sense is that most people still don't fully appreciate the close link between obesity and cancer - all the more reason to promote healthy eating and active living for all.

Obesity prevention (and treatment?) may well turn out to be the most effective cancer prevention strategy (short of smoking cessation) - looks like a whole new field for bariatric health professionals?

I guess we'd call them Bariatric Oncologists?

AMS
Edmonton, Alberta

Does Belly Fat Beget Belly Fat?

Obesity is a chronic disease and it seems that the heavier you get, the easier it is to put on even more weight.

I can think of many reasons why this may happen: less activity as you get heavier, more "emotional" eating, poorer sleep, to just name a few.

But here is a new idea: fat cells themselves may produce a substance that helps you grow even more fat cells.

This may indeed be the case, according to a study by Kaiping Yang and colleagues from the University of Western Ontario, London, Ontario published last month in the FASEB Journal.

The study was about Neuropeptide Y (NPY), a potent stimulator of hunger. Yang and colleagues not only found that in mouse and rat models of obesity, visceral fat cells can produce NPY, but also that NPY can promote the proliferation of adipocyte precursor cells via the Y1 receptor.

In fact NPY levels in visceral fat tissue were 6-fold higher in an early-life programmed rat model of increased visceral adiposity, but also more than 2-fold higher in visceral fat tissue of obese Zucker rats.

It turns out that at least in rodents, belly fat itself may be a risk factor for even more belly fat.

Would not surprise me if the same was true for humans.

An interesting question is whether or not the NPY made by fat cells can actually enter the brain to stimulate hunger, and thus, cause the animals (and humans?) to eat more - thereby creating a true vicious cycle.

Certainly an intriguing (although somewhat depressing) hypothesis.

AMS
Edmonton, Alberta

Time to Limit Weight Gain in Pregnancy?

Regular readers of my blog will have noticed several previous postings on the issue of maternal obesity and health risk for mother and infant.

This issue seems to be developing into a really "hot topic", at least judging from the flurry of articles in the most recent alerts from CON/McMaster University's OBESITY+ services.

The first was a nested case-control study comparing 251 mothers who developed gestational diabetes to matched normal controls, both selected from a multiethnic cohort of 14,235 women. In this study, Monique Heddersen and colleagues from Kaiser Permanente, Oakland, CA, demonstrated that women who gained significant amount of weight in the five years preceding their pregnancy, had a 2.5-fold higher risk of GDM compared to women with stable weight. Gestational diabetes has been linked to increased birth weights and later risk of obesity in the offspring (American Journal of Obstetrics and Gynecology, April 2008).

In the same issue of AJOG, Holly Hull from Columbia University, New York, NY, compared body weight and composition (air-displacement plethysmography) in 33 neonates born to mothers with a normal pregravid BMI to 39 neonates born to overweight/obese mothers with normal glucose tolerance. Babies born to normal BMI mothers had significantly less total and relative fat and more fat-free mass than babies born to overweight/obese mothers. Although preliminary, the authors interpret these data to suggest (and I agree) that the antecedents of future disease risk (eg, cardiovascular disease, diabetes, and obesity) occur early in life.

So what, if anything, can we do about this?

That question was addressed by Wolff and colleagues from the University of Copenhagen, who performed a randomized controlled trial in 50 obese mothers (pre-pregnancy BMI around 35) with or without restriction of gestational weight gain to 6-7 kg by ten 1-h dietary consultations. Not only did the women in the intervention group successfully limit their energy intake to restrict gestational weight gain to 6.6 kg (vs. a gain of 13.3 kg in the control group) but this was associated with a significantly reduced fasting glucose and insulin levels in the intervention group with no apparent harm to the babies. Thus, restriction of gestational weight gain in obese women is achievable and reduces the deterioration in the glucose metabolism. (International Journal of Obesity, March 2008)

Together these studies clearly support the importance of addressing obesity in mothers before and during pregnancy - an intervention that will hopefully prove beneficial to both mother and child.

So while weight management should probably soon become part of routine prenatal care, I do wonder how long it will take before we start seeing a whole new wave of "weight-loss-in-pregnancy" products and services from the ever vigilant and enterprising weight-loss industry.

Hopefully not too soon!

AMS
Edmonton, Alberta

Preventing Weight Gain is the First Step in Obesity Management

Overweight is the result of normal-weight people gaining weight.

Obesity is the result of overweight people gaining more weight.

Severe obesity is the result of people with obesity gaining even more weight.

The first step, common to both obesity prevention and treatment, is to stop further weight gain.

In fact, simply preventing weight gain at any weight may be preferable to losing weight just to gain it back. The more often you lose weight and gain it back, perhaps, the worse the consequences.

At least that is the message of a recent paper by Anne Claire Vergnaud and colleagues from the Centre de Recherche en Nutrition Humaine Ile-de-France, Bobigny, France, who studied the relationship between weight fluctuations and the risk for metabolic syndrome (International Journal of Obesity).

Metabolic syndrome status was assessed at baseline (1994/1995) and at the end of follow-up (2001/2002) in 3553 middle-aged subjects. Weight fluctuations were estimated with four weight measures during follow-up. Risk for developing metabolic syndrome was highest in the tertile with the greatest weight fluctuations, independent of whether these subjects gained weight overall or not. Of course, subjects who only gained weight (with no recorded losses) also had a higher risk than individuals whose weight did not change at all.

As in several previous studies on this issue (cited in the paper), it appears that losing and regaining weight (weight fluctuation) is worse than not losing weight at all.

Obviously, these findings have important implications for both public health messaging and clinical management. Although in both cases we propagate and promote "weight-loss" messages, the reality is that very few people who lose weight keep it off. This is true both for self-directed attempts as well as commercial weight-loss programs.

Sadly, even with clinical treatments (including obesity surgery), a substantial proportion of patients fail to keep the weight off, but indeed, success is greater the more intense the treatment and follow-up.

Given this poor success of weight-loss attempts, I cannot but wonder whether recommending weight loss to anyone who is overweight or obese is as beneficial as it is made out to be. This would be particularly true for people with what I prefer to call Stage 0 obesity.

Perhaps, with the exception of treatments with well-documented long-term outcomes, most people are best served with preventing further weight gain (difficult enough) rather than losing weight only to gain it back.

Clearly, the onus is on weight management programs, whether behavioural, medical or surgical, to document their long-term success in weight-loss maintenance.

Programs associated with a high rate of relapse probably do more harm than good.

Individuals with a high chance of relapse should not be subjected to weight-loss attempts without ongoing medical care and close follow-up.

While we await further research on this subject, we perhaps need to be a bit less casual about simply advising everyone with a "higher-than-normal" BMI to lose weight.

AMS
Edmonton, Alberta

Supersizing Pregnancy Care: the Dawn of Bariatric Obstetrics?

Last week's issue of the New England Journal of Medicine features an article by Susan Chu and colleagues from the US Centers for Disease Control and Prevention (Atlanta, GA) on the impact of obesity on health care during pregnancy.

Dr. Chu and colleagues examined 13,442 pregnancies (2000-2004) according to pre-pregnancy BMI. After appropriate corrections for confounders, hospital stay for delivery was significantly greater by approximately a full day among women with obesity than in normal weight women. Most of the increase in length of stay associated with higher BMI was related to increased rates of cesarean delivery and obesity-related high-risk conditions.

A higher-than-normal BMI was also associated with significantly more prenatal fetal tests, obstetrical ultrasonographic examinations, dispensed medications, telephone calls to obstetrics, and prenatal visits with physicians. Thus clearly, obesity during pregnancy is associated with increased use of health care services.

Obesity in pregnancy is not a topic that is discussed much in the media. I first became aware of the magnitude of this problem, when I was approached by the obstetrics folks from the McMaster University Hospital (Hamilton, Ontario) who found themselves looking after an increasing number of severely obese expecting mothers. This contact led to the initiation of a working group on bariatric nursing that devised protocols for looking after large and very large mothers.

I further realised the importance of this issue when I heard about the apparently close link between maternal obesity and the risk for both the mother and infant and the fact that obesity during pregnancy may set up the infant for future obesity through epigenetic programming. As I have blogged before, limiting weight gain during pregnancy in overweight and obese mothers may be a first step towards preventing childhood obesity.

Given that there are around 13,000 babies born in the Capital Health Region every year, about 10% of these to mothers with pre-pregnancy BMI>30, the finding of Dr. Chu et al., if translated to our region, could mean as many as 1,500 or so extra days in hospital for new mothers, much of this due to obesity-related risk. Obviously more screening tests, more frequent prenatal visits and more medications would add to the costs.

Clearly, the issue of increasing weights and weight gain in women of child-bearing age is a public health issue whose consequences and impact have yet to be fully appreciated.

As these issues affect both mothers and infants, it would not be a bad place to focus prevention measures for best impact.

AMS
Edmonton, Alberta

Obesity: It's all in Your Cells?

Yesterday I blogged about a remarkable Finnish twin study, in which the investigators went to the considerable trouble of finding monozygotic twin pairs who showed marked differences in body weight. The biggest predictor of weight gain in these genetically identical but weight-discordant co-twins was a markedly lower physical activity level, which in turn, declined even further as the obese co-twins packed on the pounds.

Assuming that this was not just a bunch of "lazy" co-twins, I wondered about what biological factors could possibly be causing these co-twins to be less physically activity. The answer to this question may lie in the results of another study by the same investigators in the same set of twins published in the open access journal PLoS Medicine.

In this study, Kirsi Pietiläinen and colleagues compared the genetic expression profiles in fat cells and macrophages between the obese and non-obese co-twins. Because, by design, the twins were genetically identical, they were able to normalise expression patterns for differences in genetic background, gender and age - thereby cutting through the considerable noise generally associated with expression studies.

In short, the authors found that the fat tissue from the obese co-twins showed a significant up-regulation of inflammatory pathways, significantly reduced mitochondrial DNA copy number, and disturbed mitochondrial energy metabolism—statistically most significantly, the decreased catabolism of branched-chain amino acids (BCAA). These impairments correlated with critical clinical measures of obesity including liver fat accumulation, reduced whole-body insulin sensitivity, hyperinsulinemia, hypoadiponectinemia and adipocyte hypertrophy.

In one individual, who the investigators were able to study before and after an additional weight gain of around 11 Kg over 3 years, mtDNA copy number was further reduced while serum BCAA concentrations and inflammatory activity increased even further.

Although the authors acknowledge that correlations do not prove causality, it is clear from the tone of their discussion that they believe that the metabolic derangements and low mtDNA copy count are a consequence of the obesity and are thus amenable to treatment by diet and exercise (the "politically correct" conclusion).

This is where I wonder if not the reverse may be true. I am no expert on mitochondrial biology, but I would assume that a key consequences of a reduction in mtDNA copy number is a decreased maximal capacity for oxidative phosphorylation, i.e., utilization of fat for energy production.

Assuming for a moment that these findings are also present in skeletal muscle, it would not be hard to imagine that these individuals are likely to find exercise more difficult and tiring than their co-twins with a normal mitochondrial population - less exercise means further weight gain and further decline in mitochondrial function - a nice little vicious cycle, if I ever saw one.

It is hard for me to image that in all 14 obese co-twins lack of physical activity alone was able to bring about the reduced mtDNA copy number, increased inflammation and reduced BCAA metabolism - somehow I find it easier to imagine that it was rather a malfunction in their mitochondria which significantly affected their ability to be (and enjoy being) physically active in the first place.

But of course, this is a chicken-or-egg question that cannot be resolved by the present study.

So the obvious questions now are: Can these co-twins be "rescued" by prescribing higher activity levels? How much activity will be needed to reverse these changes? And most importantly, will these co-twins stick with this prescription?

It's probably hard to enjoy exercise when there's a problem with your fuel cell.

AMS

The Faster the Food - the Greater the Risk?

This weekend, I was invited to participate in a panel discussion following a public viewing of the documentary Super Size Me.

The event was part of the University of Alberta's Centenary Celebrations and was co-hosted by the Faculty of Medicine and Dentistry's Arts & Humanities in Health & Medicine program and the Edmonton Public Library in their film series called "Good Medicine".

As a panelist, I had the opportunity to see the film again and to reflect on what the film is actually about.

Of course, given that the film shows how Morgan Spurlock super sizes himself by eating nothing but McDonald's for 30 days, this film can easily be interpreted to simply show how bad fast food is for you.

While there is no question that given its high content of fat, sugar and salt, fast food is certainly not the most nutritious food, to me, this is not what the film actually proves.

In fact, when you think about it, Morgan could have splurged on 5000 KCal a day of even the most nutritious and expensive foods for 30 days and probably have gained as much weight and felt as sick in the end. Yes, you can gain weight on healthy foods!

Even the most pricey restaurants, do not necessarily design their meals to be healthy and balanced and I am probably not the only one who has eaten over 2500 KCal in food and wine at a single meal even in restaurants featuring celebrity chefs - no shortage of fat, sugar and salt in those foods either.

So eating at McDonald's was just a cheaper way to make this film - no doubt, had Morgan eaten all his meals at a 3-star restaurant, he would have needed a much larger budget for his film. In other words - this was just a "cheap" shot at McDonald's.

Don't get me wrong - there is nothing healthy about McDonald's or most of the food you can get at any fast food chain. But the film does not prove this.

What the film does show though, is that eating 5000 KCal a day can lead to weight gain and make you feel pretty sick. What the film also shows is that this is quite easy to do on fast food. Part of this is because the food is so cheap (=affordable). But another important reason why it is so easy to overeat is because the food is designed to be eaten fast.

I have previously blogged about the notion that the problem with fast food is more the "fast" than the "food" (see my post No Time to be Thin). It is indeed very hard to significantly overeat on "slow" food. This is because, when you eat slow, you will be quite full long before you have managed to tuck away 2000 KCal at a single meal. In fact, the bulkier and greater the volume of the food (i.e. the lower the caloric density), the harder it is to eat 2000 KCal at a single meal.

In the film Morgan also criticizes McDonald's for offering to super size your order (which they have since stopped doing). This, however, is also not so different from what happens in any restaurant, where the servers are trained to offer an appetizer, salad, dessert and more wine if you don't remember to order these extra calories yourself. They will also be happy to "super size" your steak order by offering to add a lobster tail or extra cream or cheese on you baked potato.

So here is what I think the film does show:

a) eating 5000 KCal a day leads to weight gain, which in turn is likely to make you sick

b) McDonald's (and no doubt other fast food restaurants) make it easy and affordable for you to do so

c) McDonald's (and virtually every other restaurant I know of) wants you to eat more and will try any trick in the book to get you to do so

How do we deal with this - for one, we could begin by posting calories on ALL menus - hopefully a disincentive to overeating, no matter how fast or slow the food.

AMS

Heavy Cruising

After traveling exactly 3082 Nautical Miles (=3586 Statute Miles = 5707 Kilometers) in 12 days on the Sapphire Princess from Aukland to Sydney I am back in Canada having hopefully put on no more than a couple of lbs and aquired a substatial tan.

As predicted, food was abundant and rich - clearly "regular eating" and "grazing" are both doomed as weight-control strategies aboard cruise ships.

For anyone interested, here is my emperical formula for weight gain on cruise ships: ~ 0.5 to 1.5 g / Nautical Mile.

The fact that I had to deliver over 15 hrs of CME on obesity did not appear to help (facit: giving obesity lectures on cruise ships is not a viable strategy to prevent cruise-related weight gain).

Daily participation in early morning exercise classes also do not appear to have dropped weight gain to zero.

In any case, I am back, had a great time - thanks to the folks at CME@Sea (Sanjay, Gwen & Catherine), to the fellow physicians and their partners, my fellow faculty (Michael Gard, Carmelle Paisah, Peter Everett and Greg Hilderman) and of course to the entire crew of the Sapphire Princess for making this a great trip.

AMS

The Six Natural Laws of Weight Gain

With all the talk of "thrifty genes" and how our "hunter-gatherer genome" is overwhelmed by the "obesogenic" environment, it may be time to revisit my favorite theories about the "Natural Laws of Weight Gain".

This is something I came up with almost 10 years ago and have used in a lot of talks over the years. I've always wanted to put these ideas into a book but somehow never got around to it.

Simply stated, my Six Natural Laws of Weight Gain are as follows:

1. Always eat when food is around
2. Always go for the gravy
3. Always eat as fast as possible
4. Always eat as much as possible
5. Don't move if you don't have to
6. When fuel runs short, turn down the furnace

If anyone is thinking, "hey, that's me", you're probably not alone (in fact it's me too!).

If you take a minute to think about it, you'll probably recognize just how deeply these Natural Laws are engrained in our biology and culture and may realize how we've actually designed much of our environment to accommodate these laws.

Suddenly terms like "mindless eating", "fast"food restaurants, "all-you-can-eat" buffets, "poutine", "super-size it" and "couch potato" take on a whole new meaning.

While through the millennia of evolution these Natural Laws guaranteed the survival of our species, in our current obesogenic environment, they also pretty much guarantee weight gain.

As I have often pointed out in my talks: "In today's obesogenic environment, people have to develop "abnormal" behaviors to avoid gaining weight".

Doing things that came "naturally" to most of us is a surefire recipe for weight gain - in today's enviroment, fighting obesity literally means going against our "nature"! No wonder it is so hard to do.

OK, I realize that by now some of you are screaming that this must be wrong, that I am grossly oversimplifying the complex psychosociobiology of obesity, and that I am just providing obese people with an easy "excuse" to blame it all on nature.

Of course I realize that in reality things are way more complex and that there are many paths that lead to obesity ranging from childhood molestation to antipsychotics or from genetic defects to endocrine abnormalities (the list of possible causes if far longer than you may think!).

Nevertheless, I do believe that perhaps with the exception of such "special causes" the Natural Laws do provide a reasonable and useful framework for thinking about the root causes of the current obesity epidemic.

So in the next couple of weeks, I will be occasionally revisiting this theme and hope to explore some of these laws and how they apply to our current dilemma.

Perhaps the title of my book should be: "The Six Natural Laws of Weight Gain and How to Break Them"!

I wish someday to actually find time to write it - I could probably have a lot of fun with this.

AMS