Glyphosate-based herbicide exposure causes morphological and molecular dysregulation in the brown adipose tissue of ovariectomized female mice

Abstract

Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide. Recent evidence suggests that GBH exposure may disrupt lipid metabolism, predisposing individuals to metabolic diseases. Here, we aimed to evaluate the effects of GBH exposure on glucose homeostasis, plasma and hepatic lipids, and body adiposity in female mice. Additionally, we investigated whether the effects of GBH might be influenced by ovarian hormone status. Adult C57Bl/6 female mice underwent bilateral ovariectomy or SHAM operations. After 28 days, SHAM and OVX females received daily, via gavage, distilled water (vehicle; SHAM0 and OVX0 groups, respectively), containing or not 0.5 (SHAM0.5 and OVX0.5 groups) or 50 mg GBH/kg BW (SHAM50 and OVX50 groups) for 60 days. GBH exposure did not change body weight, food consumption, glucose homeostasis, white adipose tissue (WAT) and brown adipose tissue (BAT) weights, or plasma and hepatic lipid profiles in SHAM and OVX females. In contrast, the herbicide induced hypertrophy of lipid inclusions in brown adipocytes of OVX50 females. At the molecular level, it was observed that 50 mg/kg GBH exposure upregulated Ppar-γ in SHAM50 and OVX50 females. However, in SHAM50, this effect was accompanied by an augmentation in Cide-A and Ucp-1 genes, while in OVX50, by a down-regulation of Ucp-1 mRNA. In conclusion, the structural and molecular changes in the BAT of OVX50 females demonstrate that GBH exposure increased the number of low-thermogenic brown adipocytes, a condition that may impair body energy expenditure.

Keywords: Energy expenditure; Histopathological analysis; Ovariectomy; PPAR-γ; Pesticides.