Paglialunga 2015 Diabetologia

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Paglialunga S, Ludzki A, Root-McCaig J, Holloway GP (2015) In adipose tissue, increased mitochondrial emission of reactive oxygen species is important for short-term high-fat diet-induced insulin resistance in mice. Diabetologia 58:1071-80.

» PMID:25754553

Paglialunga S, Ludzki A, Root-McCaig J, Holloway GP (2015) Diabetologia

Abstract: Consuming a high-fat diet (HFD) induces insulin resistance in white adipose tissue (WAT) within 1 week. However, little is known about the initiating events. One potential mechanism that has remained largely unexplored is excessive mitochondrial emission of reactive oxygen species (ROS).

To determine the role of mitochondrial ROS emissions at the onset of insulin resistance, wild-type (WT) mice were placed on an HFD for 1 week. WAT insulin sensitivity and inflammation were assessed by western blot. In addition, we optimised/validated a method to determine ROS emissions in permeabilised WAT.

An HFD for 1 week resulted in impaired insulin signalling, increased c-Jun NH2-terminal kinase (JNK) phosphorylation and an increase in oxidative stress. These changes were associated with an increase in fatty-acid-mediated mitochondrial ROS emissions without any change in mitochondrial respiration/content. To determine that mitochondrial ROS causes insulin resistance, we used transgenic mice that express human catalase in mitochondria (MCAT) as a model of upregulated mitochondrial antioxidant enzyme capacity. MCAT mice displayed attenuated mitochondrial ROS emission, preserved insulin signalling and no inflammatory response following an HFD.

Findings from this study suggest that elevated mitochondrial ROS emission contributes to HFD-induced WAT insulin resistance.

Keywords: Amplex Red

O2k-Network Lab: CA Guelph Holloway GP, NL Maastricht Schrauwen P


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Diabetes  Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Fat  Preparation: Permeabilized tissue  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 

Coupling state: LEAK, OXPHOS  Pathway: F, N  HRR: Oxygraph-2k