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Insulin resistance (IR) and metabolic disorders are non-pulmonary adverse effects induced by fine particulate matter (PM 2.5 ) exposure. The worldwide pandemic of high fructose sweeteners and fat rich modern diets, also contribute to IR development. We investigated some of the underlying effects of IR, altered biochemical insulin action and Insulin/AKT pathway biomarkers. Male Sprague Dawley rats were subchronically exposed to filtered air, PM 2.5 , a fructose rich diet (FRD), or PM 2.5 + FRD. Exposure to PM 2.5 or FRD alone did not induce metabolic changes. However, PM 2.5 + FRD induced leptin release, systemic hyperinsulinemia, and Insulin/AKT dysregulation in insulin-sensitive tissues preceded by altered AT 1 R levels. Histological damage and increased HOMA-IR were also observed from PM 2.5 + FRD co-exposure. Our results indicate that the concomitant exposure to a ubiquitous environmental pollutant, such as PM 2.5 , and a metabolic disease risk factor, a FRD, can contribute to the metabolic disorder pandemic occurring in highly polluted locations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)