Pubertal atrazine exposure promotes adipocyte hypertrophy and hepatic steatosis in adult mice on a high-fat diet

Abstract

The herbicide atrazine (ATZ) has been implicated in metabolic disruptions. This study investigated the long-term consequences of pubertal ATZ-based herbicide exposure on the development of obesity in mice fed a high-fat diet (HFD) in adulthood. Male and female C57Bl/6 mice received ATZ (5 mg/kg) or water (control group) from postnatal day (PND) 30 to 60. Following puberty, all mice were fed a HFD for 90 days. Pubertal ATZ-based herbicide exposure increases food intake, specifically in male mice. While body weight, subcutaneous adiposity, and white adipose tissue (WAT) weights remained unchanged, ATZ-exposed male mice showed worsened adipocyte hypertrophy and upregulation of genes involved fat metabolism (Srebp-2, Ppar-γ, Cd36, and Adrp) in perigonadal WAT. Additionally, pubertal ATZ exposure exacerbated hepatic steatosis in both sexes, with increased ectopic fat accumulation in females correlating with increases in genes involved in fatty acid uptake and exportation (fatty acid transport protein 5 and microsomal triglyceride transfer protein). These findings provide new insights into the long-term metabolic consequences of pubertal exposure to ATZ, including exacerbated HFD-induced adiposity and hepatic steatosis. The observed sex-specific effects underscore the importance of considering pubertal windows of susceptibility to environmental disruptors and their potential impacts on adult health.

Keywords: Adiposity; adipocyte hypertrophy; endocrine-disrupting chemicals; hepatic steatosis; pesticides.