Obesity, a multifaceted condition influenced by various environmental factors, represents a critical public health challenge. Among these factors, 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 collaborative research is integral to the HEAL ITALIA Project (Health Extended Alliance for Innovative Therapies, Advanced Lab-research, and Integrated Approaches of Precision Medicine). Our main objectives are twofold: i) to investigate the impact of the MDC Acetamiprid, a known disruptor of adipocyte development and endocrine signaling within AT, on the homeostasis and function of microglia, the brain resident immune cells; ii) to explore the potential protective effects of the flavonoid Protocatechuic Acid (PCA) against Acetamiprid. To these aims, human adipocytes isolated from white adipose tissue biopsies, collected from bariatric patients of both genders, have been cultured and treated with Acetamiprid, PCA, or their combination. The Human Microglia Cell line Clone 3 (HMC3) has been then exposed to the conditioned media (CM) of the ATs treated as above to assess the effects of AT-derived signals on microglial immune profile, by means of gene and protein expression analyses. The findings from this study have the potential to guide future interventions targeted at preventing and counteracting the development of pathological conditions linked to both obesity and exposure to metabolic disruptors in the environment, contributing to the betterment of public health.