title: Skeletal muscle insulin resistance: role of mitochondria and other ROS sources.
abstract: At present, obesity is one of the most important public health problems in the world because it causes several diseases and reduces life expectancy. Although it is well known that insulin resistance plays a pivotal role in the development of type 2 diabetes mellitus (the more frequent disease in obese people) the link between obesity and insulin resistance is yet a matter of debate. One of the most deleterious effects of obesity is the deposition of lipids in non-adipose tissues when the capacity of adipose tissue is overwhelmed. During the last decade, reduced mitochondrial function has been considered as an important contributor to 'toxic' lipid metabolite accumulation and consequent insulin resistance. More recent reports suggest that mitochondrial dysfunction is not an early event in the development of insulin resistance, but rather a complication of the hyperlipidemia-induced reactive oxygen species (ROS) production in skeletal muscle, which might promote mitochondrial alterations, lipid accumulation and inhibition of insulin action. Here, we review the literature dealing with the mitochondria-centered mechanisms proposed to explain the onset of obesity-linked IR in skeletal muscle. We conclude that the different pathways leading to insulin resistance may act synergistically because ROS production by mitochondria and other sources can result in mitochondrial dysfunction, which in turn can further increase ROS production leading to the establishment of a harmful positive feedback loop.
authors.affiliation: Department of BiologyUniversity of Naples 'Federico II', Naples, Italy sergio.dimeo@unina.it.
authors.forename: Sergio
authors.initials: S
authors.lastname: Di Meo
authors.affiliation: Department of BiologyUniversity of Naples 'Federico II', Naples, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Iossa
authors.affiliation: Department of BiologyUniversity of Naples 'Federico II', Naples, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Venditti
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species
keywords: ROS production; ROS sources; diabetes; exercise; insulin resistance; mitochondria; obesity; oxidative stress