de Paula Xavier João Lucas, Ribeiro Paulo Roberto, Glugoski Larissa, da Silva Daniel Cesar, Dos Santos Luiza Lima, Nobre Elisene Alves Pires, Vicari Viviane Nogaroto, Scomparin Dionízia Xavier, Bonfleur Maria Lúcia, Ribeiro Rosane Aparecida
Universidade Estadual de Ponta Grossa, Ponta Grossa, PR, Brazil.
Universidade Estadual Do Oeste Do Paraná, Cascavel, PR, Brazil.
Environ Sci Pollut Res Int. 2025 Oct 2. doi: 10.1007/s11356-025-36985-1.
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.
草甘膦基除草剂（GBHs）是全球使用最广泛的杀虫剂。最近的证据表明，接触GBH可能会扰乱脂质代谢，使个体易患代谢性疾病。在此，我们旨在评估接触GBH对雌性小鼠葡萄糖稳态、血浆和肝脏脂质以及身体肥胖的影响。此外，我们研究了GBH的影响是否可能受卵巢激素状态的影响。成年C57Bl/6雌性小鼠接受双侧卵巢切除术或假手术。28天后，假手术组和去卵巢组雌性小鼠每天通过灌胃分别接受蒸馏水（载体；分别为假手术0组和去卵巢0组），其中含有或不含有0.5（假手术0.5组和去卵巢0.5组）或50 mg GBH/kg体重（假手术50组和去卵巢50组），持续60天。接触GBH并未改变假手术组和去卵巢组雌性小鼠的体重、食物摄入量、葡萄糖稳态、白色脂肪组织（WAT）和棕色脂肪组织（BAT）重量，或血浆和肝脏脂质谱。相反，该除草剂导致去卵巢50组雌性小鼠棕色脂肪细胞中的脂质包涵体肥大。在分子水平上，观察到接触50 mg/kg GBH使假手术50组和去卵巢50组雌性小鼠的Ppar-γ上调。然而，在假手术50组中，这种效应伴随着Cide-A和Ucp-1基因的增加，而在去卵巢50组中，伴随着Ucp-1 mRNA的下调。总之，去卵巢50组雌性小鼠棕色脂肪组织的结构和分子变化表明，接触GBH增加了低产热棕色脂肪细胞的数量，这种情况可能会损害身体能量消耗。
