期刊
DIABETES
卷 62, 期 9, 页码 3064-3074出版社
AMER DIABETES ASSOC
DOI: 10.2337/db12-1095
关键词
-
资金
- National Health and Medical Research Council of Australia (NHMRC) [526606]
- Danish Council for Independent Research-Medical Sciences
- Commission of the European Communities [223576-MYOAGE]
- Novo Nordisk Foundation
- Horslevfonden
- Danish National Research Foundation [10-083807, 02-512-55, 09-063656]
- Hojmosegardlegatet
- Fonden for Laegevidenskabens Fremme
- Direktor Jacob Madsen og Hustru Olga Madsens Fond
- Danish Ministry of Science, Technology, and Innovation
- Danish Council for Strategic Research [09-067009, 09-075724]
- Capital Region of Denmark
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 alpha-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据