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Insulin Resistance, Obesity and Lipotoxicity

  • Dilek YazıcıEmail author
  • Havva Sezer
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 960)

Abstract

Lipotoxicity, originally used to describe the destructive effects of excess fat accumulation on glucose metabolism, causes functional impairments in several metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. Lipotoxicity has roles in insulin resistance and pancreatic beta cell dysfunction. Increased circulating levels of lipids and the metabolic alterations in fatty acid utilization and intracellular signaling, have been related to insulin resistance in muscle and liver. Different pathways, like novel protein kinase c pathways and the JNK-1 pathway are involved as the mechanisms of how lipotoxicity leads to insulin resistance in nonadipose tissue organs, such as liver and muscle. Mitochondrial dysfunction plays a role in the pathogenesis of insulin resistance. Endoplasmic reticulum stress, through mainly increased oxidative stress, also plays important role in the etiology of insulin resistance, especially seen in non-alcoholic fatty liver disease. Visceral adiposity and insulin resistance both increase the cardiometabolic risk and lipotoxicity seems to play a crucial role in the pathophysiology of these associations.

Keywords

Lipotoxicity Insulin resistance Type 2 diabetes mellitus Obesity Fatty acids Diacylglycerol Ceramides Cytokines Endoplasmic reticulum stress 

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Faculty of Medicine, Division of Endocrinology and MetabolismKoc UniversityIstanbulTurkey
  2. 2.Faculty of Medicine, Division of Endocrinology and MetabolismKoc UniversityIstanbulTurkey

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