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Epigenetic Obesity In The Fruit Fly

sharma-obesity-drosophila1Regular readers are well aware of the considerable evidence now supporting the notion that inter-generational transmission of obesity risk through epigenetic modification may well be a key factor in the recent global rise in obesity rates (over the past 100 years or so).

Now a brief review article by Susan Ozanne from the University of Cambridge, UK, published in the New England Journal of Medicine, describes how researchers have now identified a clear and conserved epigenetic signature that is associated with obesity across species (from the fruit fly all the way to humans).

The article discusses how the transmission of susceptibility to obesity can occur as a consequence of “developmental programming,” whereby environmental factors (e.g. a high-fat diet) encountered at the point of conception and during fetal and neonatal life can permanently influences the structure, function, and metabolism of key organs in the offsprin, thus leading to an increased risk of diseases such as obesity later in life.

There is now evidence that such intergenerational transmission of disease can occur through environmental manipulation of both the maternal and paternal lines – thus, this is not something that is just a matter of maternal environment.

Thus, as Ozanne points out,

“Epigenetic mechanisms that influence gene expression have been proposed to mediate the effects of both maternal and paternal dietary manipulation on disease susceptibility in the offspring (these mechanisms include alterations in DNA methylation, histone modifications, and the expression of microRNAs).”

Work in the fruit fly has linked the effect of paternal sugar-feeding on the chromatin structure at a specific region of the X chromosome and transcriptome analysis of embryos generated from fathers fed a high-sugar diet, revealed dysregulation of transcripts encoding two proteins (one of them is called Su(var)) known to change chromatin structure and gene regulation.

Subsequent analyses of microarray data sets from humans and mice likewise revealed a depletion of the Su(var) proteins in three data sets from humans and in two data sets from mice.

Thus,

“This finding is consistent with the possibility that the depletion of the Su(var) pathway may be brought about by an environmental insult to the genome that is associated with obesity.”

Not only do these studies provide important insights into just how generational transmission of obesity may work but it may also lead to the development of early tests to determine the susceptibility of individuals to the future development of conditions like obesity or diabetes based on epigenetic signatures.

All of this may be far more relevant for clinical practice than most readers may think – indeed, a focus on maternal (and now paternal?) health as a target to reduce the risk of childhood (and adult) obesity is already underway.

This issue will certainly be a “hot topic” at the Canadian Obesity Summit in Toronto later this month.

@DrSharma
Edmonton, AB

 

 

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Pregnancy Outcomes After Bariatric Surgery

sharma-obesity-pregnancy5Pregnancy in women after undergoing bariatric surgery are by no means uncommon. There is even some evidence from case series to suggest that babies born to mothers, who have undergone surgery may be less likely to become obese or experience the cardiometabolic complications of obesity.

This risk needs to be balanced against potential risks the known adverse effects of gastric bypass surgery on the metabolism of iron, vitamin B12, and folate,

Now a paper by Karl Johansson and colleagues, published in the New England Journal of Medicine, suggests that this may well be the case.

The researchers identified 627,693 singleton pregnancies in the Swedish Medical Birth Register from 2006 through 2011, of which 670 occurred in women who had previously undergone bariatric surgery and for whom presurgery weight was documented.

They found that pregnancies after bariatric surgery, as compared with matched control pregnancies, were associated with lower risks of gestational diabetes (1.9% vs. 6.8%; odds ratio, 0.25) and a lower incidence of large-for-gestational-age infants (8.6% vs. 22.4%; odds ratio, 0.33).

These potentially beneficial outcomes for the infant were counterbalanced by a two-fold increase in the likelihood of having a small-for-gestational-age infants (15.6% vs. 7.6%; odds ratio, 2.20) and a somewhat shorter gestation (mean difference -4.5 days)

Also, the risk of stillbirth or neonatal death was 1.7% versus 0.7% (odds ratio, 2.39).

No differences were found in the frequency of congenital malformations.

Bariatric surgery was associated with reduced risks of gestational diabetes and excessive fetal growth, shorter gestation, an increased risk of small-for-gestational-age infants, and possibly increased mortality.

Thus, the authors conclude that,

“…a history of bariatric surgery was associated with reduced risks of gestational diabetes and large-for-gestational-age infants.”

Nevertheless, they do recommend increased surveillance during pregnancy and the neonatal period, as bariatric surgery may also be associated with small-for-gestational-age infants, a shorter length of gestation, and potentially an increased risk of stillbirth or neonatal death.

@DrSharma
Edmonton, AB

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Early Bird Registration For Canadian Obesity Summit Ends March 3rd

For all my Canadian readers (and any international readers planning to attend), here just a quick reminder that the deadline for early bird discount registration for the upcoming 4th Canadian Obesity Summit in Toronto, April 28 – May 2, ends March 3rd.

To anyone who has been at a previous Canadian Summit, attending is certainly a “no-brainer” – for anyone, who hasn’t been, check out these workshops that are only part of the 5-day scientific program – there are also countless plenary sessions and poster presentations – check out the full program here.

Workshops:

Public Engagement Workshop (By Invitation Only)

Pre-Summit Prep Course – Overview of Obesity Management ($50)

Achieving Patient‐Centeredness in Obesity Management within Primary Care Settings

Obesity in young people with physical disabilities

CON-SNP Leadership Workshop: Strengthening CON-SNP from the ground up (Invitation only)

Exploring the Interactions Between Physical Well-Being and Obesity

Healthy Food Retail: Local public‐private partnerships to improve availability of healthy food in retail settings

How Can I Prepare My Patient for Bariatric Surgery? Practical tips from orientation to operating room

Intergenerational Determinants of Obesity: From programming to parenting

Neighbourhood Walkability and its Relationship with Walking: Does measurement matter?

The EPODE Canadian Obesity Forum: Game Changer

Achieving and Maintaining Healthy Weight with Every Step

Adolescent Bariatric Surgery – Now or Later? Teen and provider perspectives

Preventive Care 2020: A workshop to design the ideal experience to engage patients with obesity in preventive healthcare

Promoting Healthy Maternal Weights in Pregnancy and Postpartum

Rewriting the Script on Weight Management: Interprofessional workshop

SciCom-muniCON: Science Communication-Sharing and exchanging knowledge from a variety of vantage points

The Canadian Task Force on Preventive Health Care’s guidelines on obesity prevention and management in adults and children in primary care

Paediatric Obesity Treatment Workshop (Invitation only)

Balanced View: Addressing weight bias and stigma in healthcare

Drugs, Drinking and Disordered Eating: Managing challenging cases in bariatric surgery

From Mindless to Mindful Waiting: Tools to help the bariatric patient succeed

Getting Down to Basics in Designing Effective Programs to Promote Health and Weight Loss

Improving Body Image in Our Patients: A key component of weight management

Meal Replacements in Obesity Management: A psychosocial and behavioural intervention and/or weight loss tool

Type 2 Diabetes in Children and Adolescents: A translational view

Weight Bias: What do we know and where can we go from here?

Energy Balance in the Weight- Reduced Obese Individual: A biological reality that favours weight regain

Innovative and Collaborative Models of Care for Obesity Treatment in the Early Years

Transition of Care in Obesity Management : Bridging the gap between pediatric and adult healthcare services

Neuromuscular Meeting workshop – Please note: Separate registration is required for this event at no charge

To register – click here.

@DrSharma
Edmonton, AB

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Pregnancy Weight Gain Study

Enrich logoToday’s post is for health professionals who provide care to pregnant women in their practice?

Researchers from the University of Alberta are conducting a short online survey to get a better understanding of the barriers and challenges you may experience related to gestational weight gain, and about what may help and support them to help women achieve healthy weights during pregnancy.

The researchers are also asking you to assess the strengths and limitations of the 5As of Healthy Pregnancy Weight Gain, a new resource from the Canadian Obesity Network.

This information will help to inform the development of universal strategies that promote healthy dietary intake and appropriate weight management in pregnancy and postpartum.

Your participation in this short survey is much appreciated.

Click here to take the survey.

@DrSharma
Edmonton, AB

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Are Sedentary Moms Promoting Childhood Obesity?

Edward Archer, PhD, University of Alabama Birmingham

Edward Archer, PhD, University of Alabama Birmingham

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.

For one,

“…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.”

Secondly,

“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.”

Thirdly,

“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.

@DrSharma
Calgary, AB

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