Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice
Research output: Contribution to journal › Journal article › Research › peer-review
Circulating interleukin (IL)-18 is elevated in obesity, but paradoxically causes hypophagia. We hypothesized that IL-18 may attenuate high fat diet induced insulin resistance by activating AMP activated protein kinase (AMPK). We studied mice with a global deletion of the α isoform of the IL-18 receptor (IL-18R(-/-)), fed a standard chow or high fat diet (HFD). We next performed gain of function experiments in skeletal muscle, in vitro, ex vivo and in vivo. We show that IL-18 is implicated in metabolic homeostasis, inflammation and insulin resistance via mechanisms involving the activation of AMPK in skeletal muscle. IL-18R(-/-) mice display increased weight gain, and ectopic lipid deposition, inflammation and reduced AMPK signaling in skeletal muscle. Treating myotubes or skeletal muscle strips with IL-18 activated AMPK and increased fat oxidation. Moreover, in vivo electroporation of IL-18 into skeletal muscle activated AMPK and concomitantly inhibited high fat diet-induced weight gain. In summary IL-18 enhances AMPK signaling and lipid oxidation in skeletal muscle implicating IL-18 in metabolic homeostasis.
Original language | English |
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Journal | Diabetes |
Volume | 62 |
Issue number | 9 |
Pages (from-to) | 3064-3074 |
Number of pages | 11 |
ISSN | 0012-1797 |
DOIs | |
Publication status | Published - 2013 |
ID: 47257355