Transgenerational Transmission of Metabolic Disease

If  anyone ever tells you that the current obesity epidemic can have nothing to do with genetics because “genes don’t change in a couple of generations”, it is completely fair to let them know that they probably do not know what they are talking about. Indeed, there is now overwhelming evidence showing that a variety of health problems, particularly related to metabolic diseases including obesity, can well be transmitted from generation to generation as a result of epigenetic modifications that persist in subsequent generations, even if these are no longer exposed to the “trigger” environment. Anyone who is interested in learning about how much we know about these intergenerational mechanisms, will probably want to read a recent review article on this subject by Rachel Stegemann and David Buchner, published in Seminars in Cell & Developmental Biology. In this papers the authors review examples of transgenerational inheritance of metabolic disease in both humans and model organisms and how these can be triggered by both genetic and environmental stimuli.ors As the authors note, “A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation.” They also discuss example of therapeutically targeting the epigenome (e.g. through dietary modification or exercise) to prevent the transgenerational transmission of metabolic disease. These findings have substantial implications for our attempts to prevent or even reverse the development of obesity in future generations. @DrSharma Vancouver, BC

Workshop: Intergenerational Determinants of Childhood Obesity

Today, attendees at the 4th Canadian Obesity Summit will face the tough task of choosing between a variety of workshops dealing with topics ranging from harnessing public-private partnership to promote healthy food in retail stores to patient centredness and ensuring the physical and mental well-being of individuals living with obesity (for a full list of workshops – click here) A workshop that I particularly look forward to is one on the determinants of the intergenerational transmission of obesity. As the organisers of this workshop tell us, “Studies in both animals and humans, including epidemiologic, clinical, and experimental data, have provided strong evidence implicating the intrauterine environment in downstream obesity. In recent years, significant advancements have been made regarding underlying molecular pathways and population level interventions and their effects on fetal programming of obesity.” Thus, this workshop will provide an update on the topic and focus on the interplay between obesity, gestational weight gain (GWG), lifestyle behaviours, and early life factors (parenting) that exacerbate fetal/child growth and perpetuate the intergenerational obesity cycle. Epigenetic and clinical evidence will be presented that demonstrates how perturbations during pregnancy affect fetal/infant phenotype and how early postpartum health (of mom and baby) predicts chronic disease risk later in life. The latest evidence from pregnancy and postpartum‐related intervention trials will be presented to identify avenues for clinical management and future research. For more information on this workshop – click here. @DrSharma Toronto, ON  

Obesity Weekend Roundup, April 17, 2015

As not everyone may have a chance during the week to read every post, here’s a roundup of last week’s posts: Epode’s Canada Obesity Forum Epigenetic Obesity In The Fruit Fly What Happens To Patients With Severe Obesity In Hospitals? Adolescents Undergoing Bariatric Surgery Are Severely Ill Targeting Gut Inflammation Can Reduce Insulin Resistance? Have a great Sunday! (or what is left of it) @DrSharma Frankfurt, Germany

Are Sedentary Moms Promoting Childhood Obesity?

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… Read More »

McKinsey on Obesity: Doing Something Beats Doing Nothing

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… Read More »