Adipose tissue regulates systemic energy metabolism through adipokine production as well as energy storage and energy supply to other organs in response to changes in energy status. Adipose tissue dysfunction is therefore thought to be a key contributor to the pathogenesis of a variety of metabolic disorders including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Given that insulin plays a central role in the regulation of many aspects of adipocyte function, insulin resistance in adipose tissue is implicated in the pathogenesis of metabolic disorders as a cause of adipose tissue dysfunction. The concept of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed for liver disease associated with metabolic disorders in both obese and nonobese individuals, with insulin resistance in adipose tissue likely being an important factor in its pathogenesis. This review outlines the relation between insulin resistance in adipose tissue and metabolic disorders, with a focus on the physiological relevance and mechanism of action of 3′-phosphoinositide-dependent kinase 1 (PDK1), a key kinase in insulin signaling, and its downstream transcription factor FoxO1 in adipocytes.
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We thank our present and former colleagues at the University of Shizuoka and Kobe University Graduate School of Medicine as well as all collaborators for contributions to the research described in this review. This study was supported in part by Japan Society for the Promotion of Science KAKENHI grants 15K09389, 18K08478, and 21H03355, as well as by grants from Yamaguchi Endocrine Research Foundation, Suzuken Memorial Foundation, Hyogo Science and Technology Association, Astellas Foundation for Research on Metabolic Disorders, and Japan Diabetes Foundation.
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Imi, Y., Ogawa, W. & Hosooka, T. Insulin resistance in adipose tissue and metabolic diseases. Diabetol Int 14, 119–124 (2023). https://doi.org/10.1007/s13340-022-00616-8