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Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.

Fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor antidepressant, has been shown to increase hepatic lipid accumulation, a key factor in the development of nonalcoholic fatty liver disease. Interestingly, fluoxetine has also been reported to increase peripheral serotonin synthesis. As emerging evidence suggests that serotonin may be involved in the development of nonalcoholic fatty liver disease, we sought to determine if fluoxetine-induced hepatic lipid accumulation is mediated via altered serotonin production. Fluoxetine treatment increased lipid accumulation in association with increased mRNA expression of tryptophan hydroxylase 1 (Tphl, serotonin biosynthetic enzyme) and intracellular serotonin content. Serotonin alone had a similar effect to increase lipid accumulation. Moreover, blocking serotonin synthesis reversed the fluoxetine- induced increases in lipid accumulation. Collectively, these data suggest that fluoxetine-induced lipid accumulation can be mediated, in part, by elevated serotonin production. These results suggest a potential therapeutic target to ameliorate the adverse metabolic effects of fluoxetine exposure. Key words: selective serotonin reuptake inhibitor, Fluoxetine, steatosis, nonalcoholic fatty liver disease, de novo lipogenesis, serotonin, metabolic disorder. On a montre que la fluoxetine, un antidepresseur inhibiteur selectif de la recapture de serotonine prescrit couramment, entraine une augmentation de l'accumulation de lipides hepatiques, facteur cle dans l'apparition d'une steatose hepatique non alcoolique. Il est interessant de noter que l'on a aussi rapporte que la fluoxetine entraine une augmentation de la synthese peripherique de serotonine. Comme des donnees emergentes laissent entrevoir que la serotonine pourrait jouer un role dans l'apparition de la steatose hepatique non alcoolique, nous avons cherche a etablir si l'accumulation de lipides engendree par la fluoxetine est mediee par l'intermediaire de la production de serotonine. L'administration de fluoxetine entraine une augmentation de l'accumulation de lipides en association avec une augmentation de l'expression en ARNm de la tryptophane hydroxylase 1 (Tphl, une enzyme de la synthese biologique de serotonine) et des taux de serotonine intracellulaires. La serotonine seule avait un effet similaire sur l'augmentation de l'accumulation de lipides. En outre, l'inhibition de la synthese de serotonine permettait d'inverser les augmentations de l'accumulation de lipides engendrees par la fluoxetine. Collectivement, ces donnees laissent entendre que l'augmentation de la production de serotonine pourrait participer a la mediation de l'accumulation de lipides engendree par la fluoxetine. Ces resultats laissent entrevoir qu'il pourrait s'agir d'une cible therapeutique eventuelle en vue d'attenuer les effets indesirables metaboliques de l'exposition a la fluoxetine. [Traduit par la Redaction] Mots-cles : inhibiteur selectif de la recapture de serotonine, fluoxetine, steatose, steatose hepatique non alcoolique, lipogenese de novo, serotonine, trouble metabolique., Introduction In Canada, it has been reported that 11.3% of people aged 15 and older had symptoms consistent with depression, with approximately one-third of individuals taking antidepressants to manage symptoms [...]

There is high demand in environmental health for adoption of a structured process that evaluates and integrates evidence while making decisions and recommendations transparent. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework holds promise to address this demand. For over a decade, GRADE has been applied successfully to areas of clinical medicine, public health, and health policy, but experience with GRADE in environmental and occupational health is just beginning. Environmental and occupational health questions focus on understanding whether an exposure is a potential health hazard or risk, assessing the exposure to understand the extent and magnitude of risk, and exploring interventions to mitigate exposure or risk. Although GRADE offers many advantages, including its flexibility and methodological rigor, there are features of the different sources of evidence used in environmental and occupational health that will require further consideration to assess the need for method refinement. An issue that requires particular attention is the evaluation and integration of evidence from human, animal, in vitro, and in silico (computer modeling) studies when determining whether an environmental factor represents a potential health hazard or risk. Assessment of the hazard of exposures can produce analyses for use in the GRADE evidence-to-decision (EtD) framework to inform risk-management decisions about removing harmful exposures or mitigating risks. The EtD framework allows for grading the strength of the recommendations based on judgments of the certainty in the evidence (also known as quality of the evidence), as well as other factors that inform recommendations such as social values and preferences, resource implications, and benefits. GRADE represents an untapped opportunity for environmental and occupational health to make evidence-based recommendations in a systematic and transparent manner. The objectives of this article are to provide an overview of GRADE, discuss GRADE's applicability to environmental health, and identify priority areas for method assessment and development.

Childhood obesity and diabetes are major threats to public health in the United States and abroad. In the United States, the prevalence of obesity among children and adolescents has almost [...]