05 August 2014
ABAF, anti-bacterial, anti-fungal, ANOVA, analysis of variance, AS160, Akt substrate of 160 kDa, BSA, bovine serum albumin, CM, conditioned medium, CXCL2, Chemokine (C-X-C motif) ligand 2, DMEM, Dulbecco’s modified Eagle's medium, DMSO, dimethylsulphoxide, ERK, extracellular signal-related kinase, FA, fatty acid, FBS, foetal bovine serum, GLUT, glucose transporter, GSK, glycogen synthase kinase, IKK, inhibitor κ kinase, IκBα, inhibitor κBα, IL, interleukin, iNOS, inducible nitric oxide synthase, IR, insulin resistance, IRS1, insulin receptor substrate-1, JNK, C-jun n-terminal kinase, LPS, lipopolysaccharide, mac, macrophage, MAPK, mitogen-activated protein kinase, MCP1, monocyte chemoattractant protein, NFκB, nuclear factor-κB, PI3K, phosphoinositol 3-kinase, palm, palmitate, PBS, phosphate-buffered saline, PKC, protein kinase C, PMA, phorbol myristate acetate, RIPA, radioimmunoprecipitation, SDS-PAGE, sodium dodecyl sulphate, polyacrylamide gel electrophoresis, SFA, saturated fatty acid, siRNA, small interfering RNA, T2D, type 2 diabetes, TLR, Toll-like Receptor, TNFα, tumour necrosis factor-α, UFA, unsaturated fatty acid, Fatty acid, Tumour necrosis factor-α, p38 Mitogen-activated protein kinase, Insulin resistance, Skeletal muscle, Macrophage
Palmitate-treated macrophage-conditioned medium causes myotube insulin resistance.
This involves activation of myotube p38 mitogen activated protein kinase.
Conditioned medium effects are mediated by tumour necrosis factor-α.
These effects are prevented by addition of palmitoleate.
Palmitoleate treatment of macrophages is insulin sensitising for myotubes.
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.