Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Diabetes Distress and Glycemic Control in Working People with Type 1 Diabetes—The Role of Intentional Hyperglycemia at Work

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

  3. An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Muscle α-adrenergic responsiveness during exercise and ATP-induced vasodilation in chronic obstructive pulmonary disease patients

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Intensive Lifestyle Intervention for Type 2 Diabetes-Reply

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations
Circulating interleukin (IL)-18 is elevated in obesity, but paradoxically causes hypophagia. We hypothesized that IL-18 may attenuate high-fat diet (HFD)-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 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, 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 HFD-induced weight gain. In summary, IL-18 enhances AMPK signaling and lipid oxidation in skeletal muscle implicating IL-18 in metabolic homeostasis.
Original languageEnglish
JournalDiabetes
Volume62
Issue number9
Pages (from-to)3064-74
Number of pages11
ISSN0012-1797
DOIs
StatePublished - Sep 2013

    Research areas

  • AMP-Activated Protein Kinases, Animals, Body Composition, Calorimetry, Indirect, Female, Insulin Resistance, Interleukin-18, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Skeletal, Real-Time Polymerase Chain Reaction, Receptors, Interleukin-18, Weight Gain

ID: 43146482