Effects of the neonicotinoid Acetamiprid on the adipose tissue/microglia cross-talk in obesity

Obesity, a multifaceted condition influenced by various environmental factors, represents a critical public health challenge. Dietary choices and exposure to metabolic disrupting compounds (MDCs) play pivotal roles in shaping adipose tissue (AT) functions and its crosstalk with different organs, including the brain. The present study aimed to investigate the complex interaction between the AT and microglia, the brain's immune cells, in the context of obesity and exposure to environmental toxicants, such as the insecticides neonicotinoids, which have recently emerged as harmful to human health. By employing the human microglia clone 3 (HMC3) cell line and AT-conditioned media (CM) collected from biopsies obtained from obese male and female patients, we aimed to: i) assess the effects of AT-derived signals on microglial immune profiles, ii) determine the impact of molecular signals from ATs exposed to the neonicotinoid Acetamiprid (ACE) on microglia, and iii) examine possible protective effects of the flavonoid Protocatechuic Acid (PCA). We analyzed the cytokines Interleukin-6 (IL-6) and Interleukin-1β (IL-1β), crucial in central glucose homeostasis. Research studies suggest that elevated IL-6 and IL-1β in microglia during early obesity stages may counteract metabolic dysfunction. Our findings show that AT-CM from obese patients increased IL-6 and IL-1β expression in microglia. However, ACE disrupted this protective mechanism by altering AT secretions, reducing cytokine expression. Additionally, microglia exposed to CM-ACE showed increased insulin receptor (InsR) expression, indicating altered glucose metabolism. Unfortunately, PCA did not revert these effects. Overall, our data raise concerns regarding the safety of ACE for human health.