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The chemokine CXCL16 can rescue the defects in insulin signaling and sensitivity caused by palmitate in C2C12 myotubes

Bitsi, S

Authors

S Bitsi



Abstract

In obesity, macrophages infiltrate peripheral tissues and secrete pro-inflammatory cytokines that impact local insulin sensitivity. Lipopolysaccharide (LPS) and the saturated fatty acid (FA) palmitate polarise macrophages towards a pro-inflammatory phenotype in vitro and indirectly cause insulin resistance (IR) in myotubes. In contrast, unsaturated FAs confer an anti-inflammatory phenotype and counteract the actions of palmitate. To explore paracrine mechanisms of interest, J774 macrophages were exposed to palmitate ± palmitoleate or control medium and the conditioned media generated were screened using a cytokine array. Of the 62 cytokines examined, 8 were significantly differentially expressed following FA treatments. Notably, CXCL16 secretion was downregulated by palmitate. In follow-up experiments using ELISAs, this downregulation was confirmed and reversed by simultaneous addition of palmitoleate or oleate, while LPS also diminished CXCL16 secretion. To dissect potential effects of CXCL16, C2C12 myotubes were treated with palmitate to induce IR, recombinant soluble CXCL16 (sCXCL16), combined treatment, or control medium. Palmitate caused the expected reduction of insulin-stimulated Akt activation and glycogen synthesis, whereas simultaneous treatment with sCXCL16 attenuated these effects. These data indicate a putative role for CXCL16 in preservation of Akt activation and insulin signaling in the context of chronic low-grade inflammation in skeletal muscle.

Citation

Bitsi, S. (2020). The chemokine CXCL16 can rescue the defects in insulin signaling and sensitivity caused by palmitate in C2C12 myotubes. Cytokine, 133, 155154. https://doi.org/10.1016/j.cyto.2020.155154

Journal Article Type Article
Acceptance Date Jun 3, 2020
Publication Date Jun 11, 2020
Deposit Date Sep 7, 2020
Publicly Available Date Jun 12, 2021
Journal Cytokine
Print ISSN 1043-4666
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 133
Pages 155154
DOI https://doi.org/10.1016/j.cyto.2020.155154
Public URL https://rvc-repository.worktribe.com/output/1377081
Publisher URL https://doi.org/10.1016/j.cyto.2020.155154

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