Hamadan University of Medical Sciences Avicenna Journal of Medical Biochemistry 2345-4113 13 2 2025 12 31 The Association of A Sedentary Lifestyle with Glucose Metabolism and Insulin Resistance 135 142 10.34172/ajmb.2637 EN Maryam Cheraghi Bedsorakhi https://orcid.org/0009-0007-4693-7068 Fatemeh Sadat Babaei Mohammad Parsa Gholbaghi Farzane Vafaei Ebrahim Abbasi https://orcid.org/0000-0002-3405-562X REVIEW 10.34172/ajmb.2637 2025 10 12 2025 12 13 Many people, including office workers, drivers, gamers, commuters, elderly people, and pregnant women, are at risk of a sedentary lifestyle. A sedentary lifestyle is characterized by spending more than 6-8 hours a day without doing intense or moderate physical activity, such as sitting on public transport, at work, or at home. Sedentary behavior is known as the main factor in the prevalence of obesity and non-alcoholic fatty liver disease (NAFLD). A sedentary lifestyle induces insulin resistance (IR) by elevating the workload of the islets and reducing their efficiency through various pathways, including inflammation, dysregulation of glucose and lipid homeostasis, and enhancing lipid storage. Furthermore, it leads to mitochondrial dysfunction, endoplasmic reticulum stress, beta cell apoptosis, and oxidative stress. In this manuscript, we explore the possible association between sedentary lifestyle and insulin resistance to increase the knowledge about the pathophysiology of sedentary lifestyle-dependent IR in the liver. Hence, in this review article, we focused on the relationship between sedentary lifestyle and lipid and carbohydrate metabolism in the liver, which can finally lead to insulin resistance.