# Acetamiprid exerts sex-specific effects on adipose tissue of subjects with severe obesity

## TL;DR

The pesticide acetamiprid affects fat tissue differently in men and women, potentially increasing obesity-related health risks.

## Contribution

This study reveals sex-specific metabolic and inflammatory effects of acetamiprid on adipose tissue in severely obese individuals.

## Key findings

- Acetamiprid lowers PPARγ gene expression but raises protein levels, especially in men.
- Free fatty acid release increases in both sexes, while Lipoprotein Lipase decreases only in women.
- Acetamiprid promotes inflammation, mainly in women, by increasing TNF-α, NF-κB, and reactive oxygen species.

## Abstract

Neonicotinoid pesticides, including acetamiprid (ACE), are widely used in agriculture and pose increasing concerns due to their persistence in the environment and potential human exposure mainly through diet. Available evidence suggests that ACE may disrupt adipocyte function and promote metabolic dysfunctions such as obesity; however, there is limited research on how ACE negatively affects adipose tissue (AT) in men and women. This study utilizes an ex vivo translational model to clarify the sex-specific effects of ACE on AT metabolic and inflammatory profile of a vulnerable human substrate, such as the visceral AT of subjects with severe obesity.

Twenty-four subjects with severe obesity (11 men and 13 women) undergoing bariatric surgery were recruited from St. Andrea University Hospital (Rome, Italy). Visceral adipose tissue biopsies were collected and either treated with ACE or left untreated for further gene and protein expression analysis by RT-qPCR and Western blot, respectively. In addition, adipocytokines secretion, reactive oxygen species production, and free fatty acid release were measured in adipose tissue culture media using commercial or in house assays.

Our findings demonstrate that ACE induces distinct sex-dependent alterations in lipid metabolism, Adipokines regulation, and inflammatory pathways. Specifically, it significantly lowers PPARγ gene expression but raises protein levels, particularly in men. Free fatty acid release increases and Hormone Sensitive Lipase (HSL) drops in both sexes, while Lipoprotein Lipase (LPL) decreases only in women. ACE also promotes inflammation mainly in women, increasing TNF-α, NF-κB, and reactive oxygen species.

These results show that the neonicotinoid ACE worsens AT dysfunction via inflammatory and metabolic pathways in a sex-specific way, likely leading to different risks of obesity-related complications. Overall, these findings provide a mechanistic basis for understanding the toxicological risk of neonicotinoids, highlighting the importance of sex-specific assessment in evaluating metabolic risks of environmental pesticide exposure.