Inhalation of diesel exhaust particulate matter accelerates weight gain via regulation of hypothalamic appetite-related genes and gut microbiota metabolism

Mice exposed to diesel exhaust particulate matter (DEPM) exhibited accelerated weight gain. Several hypothalamic genes, hormones (serum Hypothalamic-Pituitary-Adrenal (HPA) axis hormones and gastrointestinal peptide tyrosine tyrosine (PYY)), metabolites (intrahepatic triglyceride (IHTG) and fecal short-chain fatty acids (SCFAs)), and gut microbiota structure, which may influence obesity and appetite regulation, were examined. The result suggested that DEPM-induced accelerated weight gain may be associated with increased expression of hypothalamic Gamma-aminobutyric acid (GABA) type B receptor, tight junction protein, and orexin receptors, in addition with decreased IHTG and repressed HPA axis. Moreover, changes in the structure of intestinal microbiota are also related to weight changes, especially for phylum Firmicutes, genus Lactobacillus, and the ratio of relative abundance of Firmicutes and Bacteroidetes (F/B). DEPM exposure also caused widespread increase in the levels of intestinal SCFAs, the concentrations of propionic acid and isobutyric acid were associated with weight gain rate and the abundance of some bacteria. Although DEPM exposure caused changes in expression of hypothalamic serotonin, NPY, and melanocortin receptors, they were not associated with weight changes. Furthermore, no significant difference in gastrointestinal PYY and expression of hypothalamic receptors for leptin, insulin, and glucagon-like peptide 1 receptors was observed between DEPM-exposed and control mice.