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
A study by Paula Brochu and colleagues, published in Health Psychology, suggests that the often unflattering depiction of people living with obesity in the media (as in the typical images of headless, dishevelled, ill-clothed individuals, usually involved in stereotypical activities – holding a hamburger in one hand and a large pop in the other or pinching their “love handles”), may well play a role in the lack of public support for policies to address this issue.
The researchers asked participants to read an online news story about a policy to deny fertility treatment to obese women that was accompanied by a nonstigmatizing, stigmatizing, or no image of an obese couple. A balanced discussion of the policy was presented, with information both questioning the policy as discriminatory and supporting the policy because of weight-related medical complications.
The findings of the study show that participants who viewed the article accompanied by the nonstigmatizing image were less supportive of the policy to deny obese women fertility treatment and recommended the policy less strongly than participants who viewed the same article accompanied by the stigmatizing image.
Given that negative and stigmatising images of people with obesity are the rule rather than the exception in media reports about obesity, the authors suggest that simply eliminating stigmatizing media portrayals of obesity may help reduce bias and foster more support for policies to address this problem.
Readers may wish to visit the Canadian Obesity Network’s image bank Picture Perfect At Any Size of non-stigmatizing images of people living with obesity that are available for free download for educational and media purposes.
Yesterday, I blogged about the Maternal Resource Hypothesis, proposed by Edward Archer, as a driver of childhood obesity.
Today’s post is about another interesting finding by Jeffrey Galley and colleagues from Ohio State University, published in PLOS one, suggesting that maternal obesity may be associated with differences in the gut microbiome in children in early life.
The researchers compared the gut bugs from fecal samples from children 18–27 months of age (n = 77) born to obese or non-obese mothers.
At least in women of higher socioeconomic status, offspring of obese mothers showed significant differences in their gut bacteriome from those of non-obese mothers in a manner that has been previously linked to differences in weight and diet (differences were noted in the abundances of Faecalibacterium spp., Eubacterium spp., Oscillibacter spp., and Blautia spp).
While these findings were limited to women of higher socioeconomic status, the authors do not have a ready explanation for these findings.
Their best guess is that perhaps the etiology of obesity may differ between women of higher and lower socioeconomic status and it may well be that the extent to which maternal obesity confers measureable changes to the gut microbiome of offspring may differ based on the etiology of maternal obesity.
It is unlikely that dietary differences explain these findings:
“In our sample, we found no differences in the children from obese and non-obese mothers in terms of breastfeeding behavior, age at which solid foods were introduced, or the current frequency of consumption of meat, vegetables, and cereals/grains regardless of maternal SES. This suggests that diet did not explain the observed differences in the children’s gut microbiome related to maternal obesity and SES.”
Indeed, the authors are quick to point out that further research is needed to better understand the relevance of the observed differences in gut microbiome composition for weight trajectory over the life course of the offspring:
“The potential role of the gut microbiome in this intergenerational transmission of obesity risk warrants further attention. In particular, the stability of such effects into later childhood and adolescence, the clinical relevance of abundances of specific bacteria in conferring risk for obesity, and the ultimate impact of early life microbial profiles on long-term weight trajectory remains to be explicated.”
Nevertheless, these findings are intriguing in that they suggest a link between maternal obesity and the possible transmission of obesogenic microbes to their offspring.
Galley JD, Bailey M, Kamp Dush C, Schoppe-Sullivan S, & Christian LM (2014). Maternal obesity is associated with alterations in the gut microbiome in toddlers. PloS one, 9 (11) PMID: 25409177
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.