Search Results for "epigenetic"
Regular 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… Read More »
This week, I once again presented on the need for recognising obesity as a chronic disease at the annual European Society for the Study of Obesity Collaborating Centres for Obesity (EASO-COMs) in Leipzig, Germany. Coincidently, The Lancet this week also published a commentary (of which I am a co-author) on the urgent need to change the obesity “narrative”. So far, the prevailing obesity “narrative” is that this is a condition largely caused by people’s lifestyle “choices” primarily pertaining to eating too much and not moving enough, and that this condition can therefore be prevented and reversed simply by getting people to make better choices, or in other words, eating less and moving more. As pointed out in the commentary, this “narrative” flies in the face of the overwhelming evidence that obesity is a rather complex multi-factorial heterogenous disorder, where long-term success of individual or population-based “lifestyle” interventions can be characterised as rather modest (and that is being rather generous). This is not to say that public health measures targeting food intake and activity are not important – but these measures go well beyond “personal responsibility” ” The established narrative on obesity relies on a simplistic causal model with language that generally places blame on individuals who bear sole responsibility for their obesity. This approach disregards the complex interplay between factors not within individuals’ control (eg, epigenetic, biological, psychosocial) and powerful wider environmental factors and activity by industry (eg, food availability and price, the built environment, manufacturers’ marketing, policies, culture) that underpin obesity. A siloed focus on individual responsibility leads to a failure to address these wider factors for which government policy can and should take a leading role. Potential health-systems solutions are also held back by insufficient understanding of obesity as a chronic disease and of the necessary integration across specialties.“ It is also important to recognise that the prevailing “lifestyle” narrative plays a major role in the issue of weight-bias and discrimination: “Behind every obesity statistic are real people living with obesity. The prevailing narrative wrongly portrays people with obesity in negative terms as “guilty” of obesity through “weakness” and “lack of willpower”, succumbing to the siren call of fast and other poor food choices. This narrative leads to stigmatisation, discrimination—including in health services, employment, and education—and undermines individual agency.“ Thus, it is time to change this narrative: “If the narrative is instead reframed around individuals at risk of… Read More »
Continuing with citations from my article in Obesity Reviews on an aeteological framework for assessing obesity, we now turn to the importance of metabolic rate: Any assessment of obesity should begin with an estimate of energy requirement – specifically recognizing that any decrease in metabolic rate, without a corresponding decrease in energy intake and/or increase in activity will result in weight gain. Thus, in anyone presenting with weight gain, without any notable change in energy intake or activity levels, it is safe to assume that the only explanation can be a reduction in energy metabolism. As a rule of thumb: the lower the total energy requirements, the greater the risk of obesity (simply stated: over‐eating is less likely for someone who needs 4000 kcal d−1 than for someone who needs 1500 kcal d−1). In sedentary individuals, resting metabolic rate is responsible for dissipating the vast majority of daily ingested calories (60–75%) and is therefore a key determinant of energy expenditure. Thus, even a small, sustained percentage reduction in resting metabolic rate, without a compensatory adjustment of energy intake or activity, can account for a large cumulative caloric excess over time (e.g. an unbalanced 3% reduction in resting metabolic rate in an individual with a total energy expenditure of 1800 calories can lead to a caloric excess of 32.4 kcal d−1, which can translate into 972 kcal excess per month). Numerous factors can determine and/or affect metabolic rate. These include genetic and epigenetic factors, gender, aging, neuroendocrine function, sarcopenia, metabolically active fat, certain medications and prior weight loss. Commentary: of course the numeric relationship between caloric intake and weight gain is not as straightforward as many people may think. This is because changes in caloric balance will in turn change caloric expenditure – remember, we are dealing here with physiology, not physics! Thus, a 20 kcal daily excess will only lead to weight gain until the higher body weight uses up the extra 20 kcal to maintain itself, at which point the 20 kcal are no longer in excess of demands and a new caloric balance is found (weight-gain plateau – the reverse happens with caloric restriction). Thus, to continue gaining weight, one has to continue increasing caloric intake to ensure that they stay above actual requirements. This self-limiting nature on the effect of a change in caloric intake (increase or decrease) on weight gain is often forgotten when people make simplistic assumptions that small increases in caloric intake… Read More »
Following in the footsteps of other organisations like the American and Canadian Medical Associations, the Obesity Society, the Obesity Medical Association, and the Canadian Obesity Network, this month, the World Obesity Federation put out an official position statement on recognising obesity as a chronic relapsing progressive disease. The position statement, published in Obesity Reviews, outlines the rationale for recognising obesity as a chronic disease and is very much in line with the thinking of the other organisations that have long supported this notion. In an accompanying commentary, Tim Lobstein, the Director of Policy at the World Obesity Federation notes, that recognising obesity as a disease can have the following important benefits for people living with this disease: 1) A medical diagnosis can act to help people to cope with their weight concerns by reducing their internalized stigma or the belief that their problems are self-inflicted and shameful. 2) A classification of obesity as a disease, or disease process, may help to change both the public and professional discourse about blame for the condition, the latter hopefully encouraging greater empathy with patients and raising the patient’s expectations of unbiased care. 3) Recognition of obesity as a disease may have benefits in countries where health service costs are funded from insurance schemes that limit payments for non-disease conditions or risk factors. While all of this is great, and I am truly delighted to see the World Obesity Federation come around to this statement, I do feel that the policy statement seems rather tightly locked into the notion that obesity (or at least most of it) is a disease “caused” primarily by eating too much, with the blame placed squarely on the “toxic obesogenic environment”. Personally, I would rather see obesity as a far more etiologically heterogenous condition, where a wide range of mental, biological and societal factors (e.g. genetics, epigenetics, stress, trauma, lack of sleep, chronic pain, medications, to name a few) can promote weight gain in a given individual. Although these factors may well operate through an overall increase in caloric consumption (or rather, a net increase in energy balance), they, and not the act of overeating per se must be seen as the underlying “root causes” of obesity. Thus, I tend to see “overeating” (even if promoted by an obesogenic food environment) as a symptom of the underlying drivers rather than the “root cause”. Thus, saying that obesity is primarily caused by “overeating” is… Read More »
This morning, I am presenting a plenary talk in Berlin to about 200 colleagues involved in childhood obesity prevention. The 1-day symposium is hosted by Plattform Ernährung und Bewegung e.V. (Platform for Nutrition and Physical Activity), a German consortium of health professionals as well as public and private stakeholders in public health. Although, as readers are well aware, I am by no means an expert on childhood obesity, I do believe that what we have learnt about the complex socio-psycho-biology of adult obesity in many ways has important relevance for the prevention and management of childhood obesity. Not only do important biological factors (e.g. genetics and epigenetics) act on the infant, but, infants and young children are exposed to the very same societal, emotional, and biological factors that promote and sustain adult obesity. Thus, children do not grow up in isolation from their parents (or the adult environment), nor do other biological rules apply to their physiology. It should thus be obvious, that any approach focussing on children without impacting or changing the adult environment will have little impact on over all obesity. This has now been well appreciated in the management of childhood obesity, where most programs now take a “whole-family” approach to addressing the determinants of excess weight gain. In fact, some programs go as far as to focus exclusively on helping parents manage their own weights in the expectation (and there is some data to support this) that this will be the most effective way to prevent obesity in their offspring. As important as the focus on childhood obesity may be, I would be amiss in not reminding the audience that the overwhelming proportion of adults living with obesity, were normal weight (even skinny!) kids and did not begin gaining excess weight till much later in life. Thus, even if we were somehow (magically?) to completely prevent and abolish childhood obesity, it is not at all clear that this would have a significant impact on reducing the number of adults living with obesity, at least not in the foreseeable future. Let us also remember that treating childhood obesity is by no means any easier than managing obesity in adults – indeed, one may argue that effectively treating obesity in kids may be even more difficult, given the the most effective tools to managing this chronic disease (e.g. medications, surgery) are not available to those of us involved in… Read More »