Abstract
Pollutants are suspected to contribute to the etiology of obesity and related metabolic disorders. Apart from occupational exposure which concerns a subset of chemicals, humans are mostly exposed to a large variety of chemicals, all life-long and at low doses. Food ingestion is a major route of exposure and it is suggested that pollutants have a worsened impact when combined with a high-fat diet. In the experimental studies described herein, we aimed to add further evidence on the metabolic impact of food pollutants using a recently set up model in which mice are life-long fed a high-fat/high-sucrose diet (HFSD) with/without common food pollutants shown to exhibit metabolic disrupting activities. Specifically, this mixture comprised bisphenol A, dioxin, polychlorobiphenyl PCB153, and phthalate and was added in HFSD at doses resulting in mice exposure at the Tolerable Daily Intake dose range for each pollutant. We herein focused on the 7-week-old females which exhibited early signs of obesity upon HFSD feeding. We observed no signs of toxicity and no additional weight gain following exposure to the mixture but alleviated HFSD-induced glucose intolerance in the absence of alteration of gluconeogenesis and steatosis. It suggested that the observed metabolic improvement was more likely due to effects on muscle and/or adipose tissues rather than on the liver. Consistently, female mice exhibited enhanced lean/fat mass ratio and skeletal muscle insulin sensitivity. Moreover, expression levels of inflammatory markers were reduced in adipose tissue at 7 but enhanced at 12 weeks of age in agreement with the inverse alterations of glucose tolerance observed at these ages upon pollutant exposure in the HFSD-fed females. Collectively, these data suggest apparent biphasic effects of pollutants upon HFSD feeding along with obesity development. These effects were not observed in males and may depend on interactions between diet and pollutants.
Highlights
Diabetes and obesity are the major public health challenge of the 21st century, with prevalence reaching epidemic proportions worldwide
To add to the complexity of the studies, some adverse effects for BPA occurred in rodents with doses lower than the Tolerable Daily Intake (TDI) reference dose [17], and experimental studies showed that a high fat diet could amplify the adverse metabolic effects of BPA in rats [18] and PCB153 in mice [19]
With high-fat/high-sucrose diet (HFSD), the onset of obesity was gradual in our experimental model and was set up by week 12 in females with a 40% increase in body weight, enhanced levels of fasting glycaemia and plasma insulin levels [25]
Summary
Diabetes and obesity are the major public health challenge of the 21st century, with prevalence reaching epidemic proportions worldwide. The term of metabolic disruptors was proposed [2] to encompass chemicals with endocrine disrupting activity and for which exposure has been linked to diabetes and obesity in epidemiologic studies [2,3,4] as well as in experimental studies [5,6,7,8]. Based on their resistance to biodegradation, synthetic chemicals are classified in persistent organic pollutants (POPs) and short-lived pollutants. To add to the complexity of the studies, some adverse effects for BPA occurred in rodents with doses lower than the TDI reference dose [17], and experimental studies showed that a high fat diet could amplify the adverse metabolic effects of BPA in rats [18] and PCB153 in mice [19]
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