In 2011, The Lancet dedicated a special issue to the topic of obesity – the general gist being that obesity is a world wide problem which will not be reversed without government leadership and will require a systems approach across multiple sectors. The Lancet also noted that current assumptions about the speed and sustainability of weight loss are wrong.
This week, The Lancet again dedicates itself to this topic with ten articles that explore both the prevention and management of obesity.
According to Christina Roberto, Assistant Professor of Social and Behavioural Sciences and Nutrition at the Harvard T H Chan School of Public Health and a key figure behind this new Lancet Series, “There has been limited and patchy progress on tackling obesity globally”.
Or, as Sabine Kleinert and Richard Horton, note in their accompanying commentary, “While some developed countries have seen an apparent slowing of the rise in obesity prevalence since 2006, no country has reported significant decreases for three decades.”
As Kleinert and Horton correctly point out, a huge part of this lack of progress may well be attributable to the increasingly polarised false and unhelpful dichotomies that divide both the experts and the public debate, thereby offering policy makers a perfect excuse for inaction.
These dichotomies include: individual blame versus an obesogenic society; obesity as a disease versus sequelae of unrestrained gluttony; obesity as a disability versus the new normal; lack of physical activity as a cause versus overconsumption of unhealthy food and beverages; prevention versus treatment; overnutrition versus undernutrition.
I have yet read to read all the articles in this series and will likely be discussing what I find in the coming posts but from what I can tell based on a first glance at the summaries, there appears to be much rehashing of appeals to governments to better control and police the food environments with some acknowledgement that healthcare systems may need to step up to the plate and do their job of providing treatments to people who already have the problem.
As much as I commend the authors and The Lancet for this monumental effort, I would be surprised if this new call to action delivers results that are any more compelling that those that followed the 2011 series.
I can only hope I am wrong.
Unfortunately, most people have rather simplistic views of genetics – either you have a gene for disease X and you get it, or you don’t have the gene for disease X and so you’re safe.
In reality, this is not at all how genetics works (with the few rare exceptions of single-gene disorders – and even there is not at all as straightforward as most people imagine).
In fact, whether or not a gene (or group of genes) actually results in a specific phenotype is highly dependent on the environment.
As a simple example: I could be genetically highly predisposed to salt-sensitivity (i.e. having a blood pressure increase on a high-salt diet) – but unless I am actually exposed to a high-salt diet, I can go my entire life without ever developing high blood pressure.
This is pretty much the case for all complex (and even some single-gene) disorders – it is only when you put the susceptible “disease gene(s)” in the wrong environment, that the gene does what it does. This is why most “nature vs. nurture” debates lead nowhere – it is virtually never one OR the other – it is mostly BOTH!
A good example of how changing environments may be important when studying the genetics of diseases is suggested in a new study by James Niel Rosenquist and colleagues, published in the PNAS.
The researchers examines the association between the FTO gene and BMI using longitudinal data from the Framingham Heart Study collected over 30 y from a geographically relatively localized sample in the US.
What they found was that the well-documented association between the rs993609 variant of the FTO (fat mass and obesity associated) gene and body mass index (BMI) varies substantially across birth cohorts, time period, and the lifecycle, with a apparently increasing impact of this gene for those born after 1942.
As the authors point out,
“Such cohort and period effects integrate many potential environmental factors, and this gene-by-environment analysis examines interactions with both time-varying contemporaneous and historical environmental influences.”
“These results suggest genetic influences on complex traits like obesity can vary over time, presumably because of global environmental changes that modify allelic penetrance.”
In other words, as the environment changes, certain genetic “phenotypes” may become more (or less) common.
It is however important to remember in this context that the term “environment” is rather broad and may include biological drivers that include changes in the epigenome, bacteriome or even virome, all of which will have substantially changed over time (and continue to change as we we speak).
On a more practical level, this is also why genetic testing for complex genetic diseases (and so-called “personalized” medicine) will likely be nothing more than a pipe dream and a money grab, at least for the foreseeable future.
Rosenquist JN, Lehrer SF, O’Malley AJ, Zaslavsky AM, Smoller JW, & Christakis NA (2015). Cohort of birth modifies the association between FTO genotype and BMI. Proceedings of the National Academy of Sciences of the United States of America, 112 (2), 354-9 PMID: 25548176
Last week, Edward Archer from the University of Alabama at Birmingham (UAB), published a paper in the Mayo Clinic Proceedings (to much media fanfare), suggesting that the primary driver of childhood obesity is the shifting of nutrient energy to fetal adipose tissue as a result of increased maternal energy availability paired with decreased maternal energy expenditure, resulting in fetal pancreatic b-cell and adipocyte hyperplasia – a theory, which Edwards labels the “maternal resource hypothesis”.
The primary process for these changes, as readers of these pages will have read before, is through epigenetic modification of DNA, which, together with other non-genetic modes of transmission including learned behaviours and environmental exposures (socioenvironmental evolution), leads to “phenotypic evolution”, which Edward describes as,
“…a unidirectional, progressive alteration in ontogeny that is propagated over multiple successive generations and may be quantified as the change over time in the population mean for the trait under examination (eg, height and obesity).”
Since the beginning of the 20th century, socioevironmental factors have significantly altered the energy balance equation for humans
“Socioenvironmental evolution has altered the evolution of human energy metabolism by inducing substantial decrements in EE imposed by daily life while improving both the quality and the quantity of nutrient-energy availability.”
“For example, as thermoneutral environments became ubiquitous, the energy cost of thermoregulation declined, and improved sanitation (eg, clean water and safer food) and vaccinations decreased the energy cost of supporting parasites (eg, fleas) and resisting pathogens (eg, communicable diseases and diarrheal infections).”
Over the past century, these developments have led to profound phenotypic changes including,
“progressive and cumulative increases in height, body stature and mass, birthweight, organ mass, head circumference, fat mass/adiposity as well as decreases in the age at which adolescents attain sexual maturity…”
Archer goes on to describe some of the many factors that may have changed in the past century, whereby, he singles out sedentariness as one of the key drivers of these developments (not surprising given Archer’s background in exercise science).
Thus, although one could perhaps make very similar arguments for any number of factor that may have changed in the past century to, in turn, affect insulin resistance and ultimately energy partitioning (change in diet, sleep deprivation, increasing maternal age, endocrine disruptors, antibiotic use, gut microbiota, medication use and many other factors I ca think of), Archer chooses to elevate sedentariness to being the main culprit.
While this may or may not be the full story, it does not change the thrust of the paper, which implies that we need to look for the key drivers of childhood obesity in the changes to the maternal-fetal (and early childhood) environment that have put us on this self-perpetuating unidirectional cycle of phenotypic evolution.
Ergo, the solution lies in focussing on the health behaviours (again, Archer emphasizes the role of physical activity) of moms.
While Archer largely focusses on maternal transmission, we should perhaps not forget that there is now some also evidence implicating a role for epigenetic modification and intergenerational transmission through paternal DNA – yes, dads are getting older and more sedentary too (not to mention fatter).
I do however agree with Edward, that this line of thinking may well have important implications for how we approach this epidemic.
“…the acknowledgment that obesity is the result of non-genetic evolutionary forces and not gluttony and sloth may help to alter the moralizing and demoralizing social and scientific discourse that pervades both public and clinical settings.”
“Future research may be most productive if funding is directed away from naive examinations of energy balance per se and redirected to investigations of interventions that alter the competitive strategies of various tissues.”
“From the standpoint of the clinician, accurate patient phenotyping (inclusive of family obstetric history and metabolic profiling) may allow the targeting of women most likely to be a part of populations that have evolved beyond the metabolic tipping point and therefore require significant preconception intervention.”
While none of this may be easier or more feasible than other current efforts, they may well point us in a different direction than conventional theories about what is driving childhood obesity.
Last week the McKinsey Global Institute, with much media fanfare, released a 120 page discussion paper titled, “Overcoming obesity: An initial economic analysis“, which estimates that the economic cost of the global obesity epidemic is upwards of $2 trillion, a number similar to the economic cost of tobacco consumption or armed conflicts.
The report identifies 74 interventions in 18 areas (ranging from policy and population health to health care) deemed to be cost effective, which, if implemented, could lead to annual savings of $1.2 billion in the UK National Health Services alone.
However, when it comes to the actual impact of these 74 strategies, the report is far more sobering in that it notes that many of these interventions are far from proven:
“The evidence base on the clinical and behavioral interventions to reduce obesity is far from complete, and ongoing investment in research is imperative. However, in many cases this is proving a barrier to action. It need not be so. We should experiment with solutions and try them out rather than waiting for perfect proof of what works, especially in the many areas where interventions are low risk. We have enough knowledge to be taking more action than we currently are.”
In other words, let’s not wait to find out what works – let’s just do something – anything (and keep our fingers crossed).
Thus, the report urges us to
“(1) deploy as many interventions as possible at scale and delivered effectively by the full range of sectors in society; (2) understand how to align incentives and build cooperation; and (3) do not focus unduly on prioritizing interventions because this can hamper constructive action.”
I can see why politicians would welcome these recommendations, as they are essentially a carte blanche to either doing nothing (we don’t have the evidence) or doing whatever they want (anything is better than nothing).
The fact that,
“Based on existing evidence, any single intervention is likely to have only a small overall impact on its own. A systemic, sustained portfolio of initiatives, delivered at scale, is needed to address the health burden.”
means that when any measure fails, it is not because it was the wrong measure but because there was either not enough of it or it was not complemented by additional measures.
Again, a free pass for politicians, who can pass whatever measures they want (based on their political ideologies or populistic pressure from their constituencies), without having to demonstrate that what they did, had any effect at all.
Of course, no report on obesity would be complete without also stressing the importance of “personal responsibility”, as if this was somehow more important for obesity than it is for diabetes, lung disease, heart disease, or any other disease I can think of.
Unfortunately, the report also includes rather nonsensical statements like,
“44 interventions bring 20% of overweight/obese Britons back to normal weight”
a sentence that defies the very chronic nature of obesity, where once established excess weight is vigorously “defended” by complex neuroendocrine responses that will counteract any change in energy balance to sustain excess body weight.
Thus, unfortunately, the authors fall into the common misconception about obesity simply being a matter of calories in and calories out, a balance that can be volitionally adjusted to achieve whatever body weight you wish to have.
Indeed, there is very little discussion in this “discussion paper” of the underlying biology of obesity, although it is acknowledged in passing:
“Even though there are important outstanding questions about diet composition, gut microbiome, and epigenetics, we are not walking blind with no sense of what to address. However, interventions to increase physical activity, reduce energy consumption, and address diet composition cannot just seek to reverse the historical trends that have left the population where it is today. For example, we cannot, nor would we wish to, reverse the invention of the Internet or the industrialization of agriculture. We need to assess what interventions make sense and are feasible in 2014.”
Will this report move governments to action? Or, even more importantly, will this report bring us any closer to reversing the epidemic or providing better treatments to people who already have obesity?
Readers may appreciate that I am not holding my breath quite yet.
Here is what we had to say about the role of exercise in weight management in our recent article published in Canadian Family Physician:
There is now a consistent body of evidence showing that exercise alone, despite a range of health benefits associated with regular exercise, results in rather modest weight loss (less than 2 kg on average).
One of the explanations is that exercise is often accompanied by an increase in sedentary activities and appetite and a decrease in dietary restraint that counteract the increased energy expenditure of exercise.
However, increased exercise has been shown to reduce visceral adiposity (even with minimal changes in body weight).
Individuals who include regular exercise and active living as part of a weight-loss program are more likely to improve their overall health and keep the weight off.22 This latter finding might be attributable to the effect of regular exercise on caloric intake rather than on caloric expenditure per se.
Exercise alone generally promotes modest weight loss; however, individuals who exercise regularly might improve their overall health independent of weight loss and are more likely to keep their weight off.