title: Palmitoleic acid prevents palmitic acid-induced macrophage activation and consequent p38 MAPK-mediated skeletal muscle insulin resistance.
abstract: Obesity and saturated fatty acid (SFA) treatment are both associated with skeletal muscle insulin resistance (IR) and increased macrophage infiltration. However, the relative effects of SFA and unsaturated fatty acid (UFA)-activated macrophages on muscle are unknown. Here, macrophages were treated with palmitic acid, palmitoleic acid or both and the effects of the conditioned medium (CM) on C2C12 myotubes investigated. CM from palmitic acid-treated J774s (palm-mac-CM) impaired insulin signalling and insulin-stimulated glycogen synthesis, reduced Inhibitor κBα and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase in myotubes. p38 MAPK inhibition or siRNA partially ameliorated these defects, as did addition of tumour necrosis factor-α blocking antibody to the CM. Macrophages incubated with both FAs generated CM that did not induce IR, while palmitoleic acid-mac-CM alone was insulin sensitising. Thus UFAs may improve muscle insulin sensitivity and counteract SFA-mediated IR through an effect on macrophage activation.
authors: Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK.
authors: Nicola A
authors: NA
authors: Talbot
authors: Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK.
authors: Caroline P
authors: CP
authors: Wheeler-Jones
authors: Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK. Electronic address: mcleasby@rvc.ac.uk.
authors: Mark E
authors: ME
authors: Cleasby
mesh_terms: D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006801:Humans; D007333:Insulin Resistance; D008262:Macrophage Activation / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects; D019308:Palmitic Acid / Q000633:toxicity; D060888:Real-Time Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D005229:Fatty Acids, Monounsaturated; C008757:palmitoleic acid; D019308:Palmitic Acid; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Fatty acid; Insulin resistance; Macrophage; Skeletal muscle; Tumour necrosis factor-α; p38 Mitogen-activated protein kinase