Bisphenol A and adiposity measures in peripubertal boys from the INMA-Granada cohort
Introduction
The childhood obesity epidemic is one of the most concerning public health challenges of the 21st century. Over 340 million children and adolescents aged 5–19 were estimated to be overweight or obese worldwide in 2016 (WHO, 2017). Overweight and obese children are likely to stay obese into adulthood and are at a higher risk of developing cardio-metabolic diseases (WHO, 2017). Despite increased awareness of the problem, recent studies indicate that childhood obesity trends have not improved and have even worsened in some countries (Friedrich, 2017; Ludwig, 2018; Skinner et al., 2018). Unhealthy dietary patterns and sedentary lifestyles are acknowledged to be the main drivers of this global epidemic; however, mounting evidence suggests that other environmental factors, such as exposure to obesogenic endocrine disrupting chemicals (EDCs), may play a role in the development of childhood obesity and metabolic disorders (Braun, 2017; Dhurandhar and Keith, 2014).
Bisphenol A (BPA) is a well-known EDC capable of disturbing hormonal homeostasis at low doses in experimental studies (Vandenberg et al., 2012). Apart from its ability to interfere with reproduction and neurodevelopment (Mustieles et al., 2018a, 2015; Peretz et al., 2014), BPA is a suspected obesogen found to increase adiposity and alter metabolism in experimental models (Valentino et al., 2016; Wassenaar et al., 2017). Despite not being biologically inert, BPA is extensively used in the manufacture of polycarbonate plastics, epoxy resin liners of canned food, some dental composite resins, medical devices, and thermal-paper receipts (Molina-Molina et al., 2019), among many other technological applications (Vandenberg et al., 2007). Diet constitutes one of the main sources of exposure, due to the leaching of BPA from packaging materials and can liners into food and beverages (Vandenberg et al., 2010). Other routes and sources such as inhalation and dermal absorption also contribute to total human exposure (Ehrlich et al., 2014; Healy et al., 2015; Michałowicz, 2014). Although BPA is rapidly metabolized and excreted in urine, chronic daily exposure explains the detection of urinary BPA in more than 90% of the general population in industrialized countries (Becker et al., 2009; Calafat et al., 2008; Casas et al., 2011; Vandenberg et al., 2010).
Obesogens are thought to promote obesity in three ways: by increasing the number of adipocytes and/or the fat storage/content in existing fat cells, by altering the energy balance towards the storage of calories (i.e., decreasing thermogenesis); or by disrupting signals that regulate appetite and satiety mechanisms (Janesick and Blumberg, 2016). In this regard, BPA has been shown to promote adipogenesis in human stem cells in vitro (Boucher et al., 2014; Ohlstein et al., 2014), mainly via estrogenic pathways. BPA can also act in the brain stimulating the appetite, leading to increased food intake by mice (Mackay et al., 2013). A recent systematic review of experimental studies in rodents concluded that early-life exposure to BPA may increase adiposity and circulating lipid levels (Wassenaar et al., 2017).
Although the experimental literature is compelling, the epidemiological evidence is less consistent and remains limited. While some reviews of studies in human adults and children have supported the role of BPA as an obesogen (Rancière et al., 2015), other researchers have been more cautious, citing challenges and inherent methodological limitations (Oppeneer and Robien, 2015) such as exposure assessment issues, confounding by diet and lifestyle patterns, the critical window of development assessed, adiposity measurement by indirect methods alone, and study design (Liu and Peterson, 2015; Oppeneer and Robien, 2015; Romano et al., 2014; Sharpe and Drake, 2013).
The peripubertal period is increasingly recognized as a window of heightened vulnerability to environmental exposures (Zawatski and Lee, 2013). It represents an understudied and particularly high-risk time for weight gain due to the synergy of physiological metabolic changes with increasing behavioral risk factors (Jasik and Lustig, 2008). Although a gradual weight gain from infancy throughout childhood is necessary for the onset of puberty, persistence of this weight gain during puberty may be a risk factor for obesity and the metabolic syndrome later in life (Lehrer, 2015).
Obesity is one of the most serious long-term health risks currently faced by children in most countries, including Spain (Sánchez-Cruz et al., 2013), and the obesogenic action of BPA is supported by an important body of experimental evidence (Wassenaar et al., 2017). Given the limited information available on this issue during peri-puberty, we undertook a study to assess the association between urinary BPA concentrations and several adiposity measures in a cohort of peripubertal boys from Granada, Southern Spain.
Section snippets
Study population
The INMA (Infancia y Medio Ambiente – Environment and Childhood) Project is a multicenter population-based cohort study composed of seven cohorts established in seven geographical areas of Spain and designed to explore the effects of exposure to environmental chemicals during pregnancy and childhood on child growth and development (Guxens et al., 2012). The INMA-Granada cohort includes 668 mother-son pairs recruited at delivery (2000–2002) at the San Cecilio University hospital in the province
Characteristics of the study population
BPA concentrations were detected in all urine samples at a wide range of concentrations, with a median (IQR) of 4.74 (2.86, 8.96) μg/L (Table 1). The mean (standard deviation [SD]) age was 9.90 (0.34) years and the BMI was 18.4 (3.49) Kg/m2 (Table 1). The vast majority (81.9%) of the boys were prepubertal, while 18% had already initiated puberty and were in Tanner stage II. The mean (SD) total daily calorie intake was 2305 (988) Kcal, similar to recommendations for boys of this age (USDA, 2010;
Discussion
In this study of peripubertal boys from the INMA-Granada Spanish cohort, urinary BPA concentrations were associated with increased BMI z-scores and a higher risk of overweight/obesity. Children with higher urinary BPA concentrations also had higher WHtR values and a greater risk of abdominal obesity. In contrast, BPA concentrations were not associated with % body fat mass. These findings suggest that BPA exposure could increase the risk of overweight and obesity, especially abdominal obesity,
Conclusions
Our findings in peripubertal boys from the Spanish INMA-Granada cohort suggest that BPA may exert an obesogenic effect during this period of development, potentially increasing the risk of overweight and obesity, especially abdominal obesity. However, these results should be interpreted with caution, given the modest sample size and the possibility of reverse causality and residual confounding by diet and lifestyle patterns.
Acknowledgments
This research would not have been achieved without the selfless collaboration of the INMA-Granada boys and families who took part in the study. The authors gratefully acknowledge editorial assistance provided by Richard Davies. This study was supported in part by research grants from the European Union Commission (H2020-EJP-HBM4EU and SOE1/P1/F0082), Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), from the Institute of Health Carlos III - supported by
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