The complex interplay between oxinflammation, mitochondrial dysfunction and lipotoxicity: focus on their role in the pathogenesis of skeletal muscle insulin resistance and modulation by dietary fatty acids

Skeletal muscle insulin resistance is pivotal in the pathogenesis of type 2 diabetes mellitus (T2DM). Oxinflammation, referred to as the coexistence of and tight relationship between inflammation and oxidative stress, along with mitochondrial dysfunction and lipotoxicity have all been implicated in the pathogenesis of skeletal muscle insulin resistance. Most importantly, these effectors of insulin resistance are able to fuel one another, thereby generating a complex vicious cycle. This review aims at providing an updated and critical overview on the intimate cross-talk between oxinflammation, mitochondrial dysfunction and lipotoxicity as key molecular mechanisms underpinning insulin resistance. Additionally, the role of dietary fatty acids in modulating the key actors of this vicious cycle and the repercussions on skeletal muscle insulin sensitivity will be discussed in detail.