| First Author | Mancini SJ | Year | 2017 |
| Journal | Mol Cell Endocrinol | Volume | 440 |
| Pages | 44-56 | PubMed ID | 27840174 |
| Mgi Jnum | J:248797 | Mgi Id | MGI:6095577 |
| Doi | 10.1016/j.mce.2016.11.010 | Citation | Mancini SJ, et al. (2017) Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation. Mol Cell Endocrinol 440:44-56 |
| abstractText | Inflammation of adipose tissue in obesity is associated with increased IL-1beta, IL-6 and TNF-alpha secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-inflammatory actions in adipose tissue, yet the mechanisms underlying this remain poorly characterised. The effect of AMPK activation on cytokine-stimulated proinflammatory signalling was therefore assessed in cultured adipocytes. AMPK activation inhibited IL-1beta-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation and downregulated MKK4/JNK and IKK/IkappaB/NFkappaB signalling. AMPK activation inhibited TNF-alpha-stimulated IKK/IkappaB/NFkappaB signalling but had no effect on JNK phosphorylation. The JAK/STAT3 pathway was also suppressed by AMPK after IL-6 stimulation and during adipogenesis. Adipose tissue from AMPKalpha1(-/-) mice exhibited increased JNK and STAT3 phosphorylation, supporting suppression of these distinct proinflammatory pathways by AMPK in vivo. The inhibition of multiple pro-inflammatory signalling pathways by AMPK may underlie the reported beneficial effects of AMPK activation in adipose tissue. |
