Exposure to Nanoscale Particulate Matter from Gestation to Adulthood Impairs Metabolic Homeostasis in Mice

Nicholas C Woodward,Todd E Morgan,Jaana Hartiala,Heidi Kocalis,Amanda L Crow,Sam Epstein,Jesus A Araujo,Yang Zhang,Ishwarya Sankaranarayanan,Gajalakshmi Ramanathan,Omid Akbari,Richard Johnson,Sebastien G Bouret,Arian Saffari,Constantinos Sioutas,Caleb E Finch,Hooman Allayee

doi:10.1038/s41598-018-37704-2

Abstract

Emerging evidence from epidemiological and animal studies suggests that exposure to traffic-related air pollutants and particulate matter less than 2.5 µm in diameter (PM2.5) contributes to development of obesity and related metabolic abnormalities. However, it is not known whether nanoscale particulate matter (nPM) with aerodynamic diameter ≤200 nm have similar adverse metabolic effects. The goal of the present study was to determine the effects of prenatal and early life exposure to nPM on metabolic homeostasis in mice. C57BL/6 J mice were exposed to nPM or filtered air from gestation until 17 weeks of age and characterized for metabolic and behavioral parameters. In male mice, nPM exposure increased food intake, body weight, fat mass, adiposity, and whole-body glucose intolerance (p < 0.05). Consistent with these effects, male mice exposed to nPM displayed alterations in the expression of metabolically-relevant neuropeptides in the hypothalamus and decreased expression of insulin receptor signaling genes in adipose (p < 0.05). There were no differences in exploratory behavior or motor function, fasting lipid levels, or the inflammatory profile of adipose tissue. Our results provide evidence that chronic nPM exposure from gestation to early adulthood in male mice promotes metabolic dysregulation in part through modulation of feeding behavior and in the absence of an obesogenic diet.

Highlights

Suggest that exposure to ambient air pollution, including during critical periods of development, may contribute to obesity in early life and its metabolic consequences later in adulthood
As a first step towards characterizing the effects of ultrafine particulate matter on metabolic homeostasis in mice, we carried out an exposure protocol starting at gestation and continuing through young adulthood
Energy expenditure compared to control mice (Fig. 1C and Table 1). These results suggest that the higher body weight observed in male mice exposed to nanoscale particulate matter (nPM) was primarily due to increased accumulation of adipose tissue

Summary

Introduction

Suggest that exposure to ambient air pollution, including during critical periods of development, may contribute to obesity in early life and its metabolic consequences later in adulthood. Mouse studies focused on obesity have evaluated the effects of regional fine particulate matter, defined less than 2.5 μm in diameter (PM2.5), with or without high fat feeding These studies have shown that exposure to PM2.5 modulates adiposity, with respect to visceral fat accumulation, the development of glucose intolerance and other related metabolic abnormalities[20,21,22]. Within the size spectrum of PM2.5, nanoscale particulate matter (nPM) with aerodynamic diameter ≤200 nm, which are emitted primarily through vehicular emissions and other combustion sources, may be of particular relevance to obesity and metabolic health These nanoscale particles contain a high content of redox-cycling organic chemicals and can have higher biological activity than larger particulates due to their higher surface area-to-mass ratio[24]. The goals of this study were to determine the effects of nPM exposure on metabolic homeostasis in mice

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Conclusion