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Obesogens and obesity-An alternative view?

2013; Wiley; Volume: 21; Issue: 6 Linguagem: Inglês

10.1002/oby.20373

1930-739X

Richard M. Sharpe, Amanda J. Drake,

Consumer Attitudes and Food Labeling

ObesityVolume 21, Issue 6 p. 1081-1083 PerspectivesFree Access Obesogens and obesity—An alternative view? Richard M. Sharpe, Corresponding Author Richard M. Sharpe MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UKMRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK. E-mail: [email protected]Search for more papers by this authorAmanda J. Drake, Amanda J. Drake Endocrinology Unit, University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UKSearch for more papers by this author Richard M. Sharpe, Corresponding Author Richard M. Sharpe MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UKMRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK. E-mail: [email protected]Search for more papers by this authorAmanda J. Drake, Amanda J. Drake Endocrinology Unit, University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UKSearch for more papers by this author First published: 20 March 2013 https://doi.org/10.1002/oby.20373Citations: 28 Funding agencies: This work was supported by Grant G1100358 from the UK Medical Research Council and by a Scottish Senior Clinical Fellowship. Disclosure: RMS is a member of a Science Advisory Panel for BASF, but this does not involve work on obesogens or the chemicals referred to in this article. AJD has nothing to disclose. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract It is accepted that diet is a major contributor to the obesity epidemic, but environmental ‘obesogenic’ chemicals have also been suggested recently as playing a role, based on in vitro, animal and epidemiological studies. Using two such ‘obesogen’ examples (bisphenol A, certain phthalate esters), we argue that their association with obesity and obesity-related disorders in humans could be circumstantial, and thus non-causal, because a Western style diet increases exposure to these compounds. This possibility needs to be addressed before further (confounded) epidemiological studies on ‘obesogens’ are undertaken. The prevalence of obesity more than doubled between 1980 and 2008 worldwide, so that by 2008, 10% of men and 14% of women in the world were obese (body mass index, BMI ≥ 30 kg/m2) and at least 2.8 million people die each year as a result of being overweight or obese (1). There is a huge incentive to gain a better understanding of the causes of this obesity epidemic. Any improvement in our ability to prevent obesity and its associated health consequences would bring health benefits for individuals and improve population welfare. It would also have a significant impact on health and welfare costs—the estimated annual medical costs of obesity in 2008 were $147 billion in the USA alone (2). Adiposity is highly heritable, with an estimated genetic contribution to BMI of 20-84%. However, although genome-wide association studies have identified many genomic regions associated with obesity, common forms of obesity are highly polygenic, with each variant contributing very small effects (3). But clearly our genetic make-up has not changed dramatically over the last half century, so what has? The explanations most commonly advanced for the obesity epidemic are increased calorie intake and decreased energy expenditure; however in reality, many “environmental” factors are likely to contribute—diet, exercise, economic, and psychosocial influences to name but a few (4). Environmental factors may have important interactions with some of the “obesity gene” variants (5). A new hypothesis has emerged in recent years: the suggestion that environmental chemicals (termed obesogens) promote obesity. This is based on several lines of evidence, including numerous epidemiological studies in man (6). Further concerns have been raised by the increasing body of evidence for a lasting effect of the pre- and/or postnatal environment on the predisposition to later obesity (7). The suggestion that exposure to obesogens during early life is associated with such developmental “programming” effects has led to the “developmental obesogen hypothesis” (8). One feature of the implicated chemicals is that they are ubiquitous in our environment, so we are all exposed to greater or lesser degrees and, importantly, exposure has increased over recent years in parallel with the obesity epidemic (4). Examples include compounds used in various types of plastics, such as phthalate esters and bisphenol A, and long-lived polychlorinated organic pollutants (POPs) such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), that are now mainly banned, but which have accumulated in the food-chain. Substantial resources are being directed toward addressing the impact of calorie over-consumption and inactivity on the human obesity epidemic. However, if environmental obesogens are also important contributing factors, alternative public health strategies aimed at reducing exposure are clearly needed. But how good is the evidence for this and what exactly does it comprise? Studies have suggested that “environmental obesogens” can target cellular processes that are important in regulating metabolic function (9). These include peroxisome proliferator (PPAR)-modulated pathways (9, 10), adipogenesis (11, 12), altered pancreatic β cell mass/function (13), and altered hypothalamic circuits that modulate energy balance (17). Other studies have shown that exposure of rodents in vivo to tributyl tin (18) or to bisphenol A (19) can induce features of the metabolic syndrome including increase in weight/obesity. However, whether human exposure is sufficient to induce such effects is unknown, as dietary exposure of rodents to more human-relevant doses (of bisphenol A) does not induce such effects (20). Indeed, perhaps the biggest issue for the obesogen hypothesis is whether humans are exposed to sufficient amounts of these obesogens, either for individual chemicals or for their combination in “mixtures,” to exert biological effects of the sort that have been shown in vitro or in experimental animal studies. Therefore, time to consider the epidemiological evidence. There are now several cross-sectional epidemiological studies showing a significant association between concurrent urinary levels of bisphenol A and obesity (21, 22) or obesity-related disorders, e.g. type II diabetes (23) although a very recent analysis using the same source material has questioned this (27). Other studies have shown a similar association of obesity with phthalate exposure (28). None of the “positive” studies show cause and effect and, since obesity is a long-term disorder, the association with concurrent exposure has obvious limitations. Nevertheless, such evidence cannot simply be dismissed, as it is clearly telling us something fundamental. The question is what is it telling us? The obesogen hypothesis proposes that our exposure to these compounds can short-circuit aspects of appetite and/or metabolic control pathways and thus promote the development of obesity. This has all the attractions of any novel discovery/hypothesis. However, we propose that there may be an alternative explanation. One of the most commonly advanced reasons for the increase in prevalence of obesity is consumption of a “Western” fast-food, high fat, energy-rich diet. If such a diet also determines our level of exposure to obesogens, then increased consumption of this diet would increase the risk of becoming obese at the same time as increasing exposure to environmental obesogens. Thus, the latter would become associated (non-causally) with the obesity by default. There is reasonable, if indirect, supporting evidence for this: diet accounts for >95% of population level exposure to bisphenol A (32) and switching from a modern fast-food/processed/packaged food diet to the same ingredients but freshly sourced and unpackaged lowered urinary levels of bisphenol A by 66% (33). The same study (33) showed that exposure to the most ubiquitous phthalate (diethylhexyl phthalate) were similarly lowered by >50%, and other studies using fasting (34) have shown that diet seems to be the predominant source of human exposure to this and several other phthalates. Arguably, more solid evidence in favor of the obesogen hypothesis can be derived from prospective and cross-sectional studies that have shown positive associations between obesity and exposure to POPs (8, 9, 35). However, similar confounding with diet may also be present, as described above for bisphenol A and phthalates. POPs are lipophilic and accumulate in animal fat (and therefore in the food chain), and this is our main route of exposure (36, 37). Consequently, it is reasonable to speculate that a modern “poor” high-fat diet results in increased exposure to POPs (36, 37), although this needs to be formally tested. Other factors may also apply, for example there is evidence that POPs might increase thermogenesis and thus reduce weight gain (38), complicating interpretation of association data between POP exposure and bodyweight. Poor diet and the imbalance between energy intake and expenditure are key factors in the obesity epidemic, and whilst this remains the major problem that must be addressed if the trend is to be reversed, understanding whether there is any role for environmental obesogens is of great public health importance. The only direct supporting evidence in humans is the epidemiological evidence, but if poor diet is also responsible for higher obesogen exposure, then this evidence is intrinsically confounded. Therefore, we suggest that the next step is to determine the role that poor diet plays in determining obesogen exposure, before embarking on further epidemiological association studies which may be confounded. Only in this way will it be possible to show whether or not there is any substance to the obesogen hypothesis. References 1 World Health Organisation: The challenge of obesity – quick facts and figures http://www.euro.who.int/en/what-we-do/health-topics/noncommunicable-diseases/obesity/facts-and-figures. (accessed 19th October 2012). 2Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff 2009: 28: w822- w831. 3Fall T, Ingelsson E. Genome-wide association studies of obesity and metabolic syndrome. 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