Endocrine Abstracts

Adipose tissue inflammation may be an important mechanism in the development of systemic insulin resistance, such that modulation of this system may be a therapeutic target for type 2 diabetes and obesity-related disorders. AMPK has anti-inflammatory properties, yet the anti-inflammatory actions of AMPK in adipocytes remain poorly characterised. We questioned whether AMPK activation influences pro-inflammatory responses in cultured adipocytes in basal and stimulated conditions. Expression of pro-inflammatory chemokines and cytokines were studied in SW872 cells (human adipocyte cell line). Adipocytes were exposed to the AMPK activators AICAR (1 mM, 1 h) or A769662 (100–300 μM, 30 min) and subsequently stimulated with pro-inflammatory mediators TNF-α (10 ng/ml, 8–24 h) or Interleukin-1β (IL-1β, 10 ng/ml, 6 h). Effects on mRNA expression of MCP-1, CXCL-1, CXCL-10 and IL-6 were examined by RT-PCR. Immunoblotting confirmed AMPK activation with phosphorylation of AMPK-Thr172 and downstream ACC-Ser79. AICAR, a non-specific AMPK activator, decreased basal expression of MCP-1 (90%), CXCL-1 (71%) and CXCL-10 (93%) after 24 h and attenuated TNF-α- and IL-1β- stimulated increases in gene expression of CXCL-1 (IL-1β 11.7 vs AICAR+IL-1β 3.3 fold increase) and CXCL-10 (IL-1β 39.6 vs AICAR+IL-1β 4.2 fold increase). The selective AMPK activator A769662 however increased basal IL-6 (28 fold) and MCP-1 (3.8 fold) and exacerbated TNF-α- and IL-1β- induced IL-6 (TNF-α 5.8 vs A769662+TNF-α 29.8 fold increase) and MCP-1 gene expression (TNF-α 2.5 vs A769662+TNF-α 5.3 fold increase). Conversely, A769662 decreased basal (52%) and agonist-stimulated increases in CXCL-10 gene expression (TNF-α 11.5 vs A769662+TNF-α 0.56 fold change). These data demonstrate that pharmacological activators of AMPK influence pro-inflammatory responses in human adipocytes. Depending on the signalling pathways targeted by the activators, responses seem to differ. Selectively activating AMPK with A769662 promotes inflammation by increasing expression of cytokines. The fact that AMPK activators influence basal cytokine expression and production, suggests that these processes are constitutively active in adipocytes. Our findings highlight an interaction between AMPK and inflammation.