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Insulin resistance in obesity: an overview of fundamental alterations

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Abstract

Obesity is a major health risk factor, and obesity-induced morbidity and complications account for huge costs for affected individuals, families, healthcare systems, and society at large. In particular, obesity is strongly associated with the development of insulin resistance, which in turn plays a key role in the pathogenesis of obesity-associated cardiometabolic complications, including metabolic syndrome components, type 2 diabetes, and cardiovascular diseases. Insulin sensitive tissues, including adipose tissue, skeletal muscle, and liver, are profoundly affected by obesity both at biomolecular and functional levels. Altered adipose organ function may play a fundamental pathogenetic role once fat accumulation has ensued. Modulation of insulin sensitivity appears to be, at least in part, related to changes in redox balance and oxidative stress as well as inflammation, with a relevant underlying role for mitochondrial dysfunction that may exacerbate these alterations. Nutrients and substrates as well as systems involved in host–nutrient interactions, including gut microbiota, have been also identified as modulators of metabolic pathways controlling insulin action. This review aims at providing an overview of these concepts and their potential inter-relationships in the development of insulin resistance, with particular regard to changes in adipose organ and skeletal muscle.

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Authors and Affiliations

  1. Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy

    Rocco Barazzoni & Gianluca Gortan Cappellari

  2. Azienda Sanitaria Universitaria Integrata di Trieste (ASUITS), Trieste, Italy

    Rocco Barazzoni & Gianluca Gortan Cappellari

  3. Department of Medical Biotechnology and Translational Medicine, Centre for Study and Research on Obesity, University of Milan, Via Vanvitelli, 32, 20129, Milan, Italy

    Maurizio Ragni & Enzo Nisoli

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  1. Rocco Barazzoni
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  2. Gianluca Gortan Cappellari
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  3. Maurizio Ragni
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Barazzoni, R., Gortan Cappellari, G., Ragni, M. et al. Insulin resistance in obesity: an overview of fundamental alterations. Eat Weight Disord 23, 149–157 (2018). https://doi.org/10.1007/s40519-018-0481-6

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