Annexin A1 (AnxA1), an endogenous glucocorticoid regulated protein, is a pivotal homeostatic regulator of the magnitude of the inflammatory response. We have previously demonstrated that plasma AnxA1 protein is significantly inversely correlated with waist to hip ratio (P=0.017). Given that low-level systemic inflammation is seen in metabolic syndrome-associated chronic pathologies, here, we investigate if AnxA1 is also involved in the regulation of adipose tissue inflammation. One day post confluent pre-adipocytes and mature SGBS adipocytes were collected for RT-PCR gene expression of ANXA1 and its receptors, formyl peptide receptor 1 (FPR1) & formyl peptide like receptor (FPRL1). Normalised relative expression of ANXA1 was found to be up-regulated in mature adipocytes when compared to pre-adipocytes (P= 0.003). To mimic the relative hypoxia found in the fat tissue of the obese, pre-adipocytes were treated with 4, 8 and 24 hour hypoxia treatment (1% O2) where ANXA1 was found to be down-regulated (P=0.006, P=0.002, P=0.001, respectively). There was no significant difference in the expression of ANXA1 during hypoxia treatments in mature adipocytes. Adipocyte expression of adiponectin gene was down regulated after 24 hrs of hypoxia treatment (P=0.024) whilst expression of leptin gene was up-regulated following 8 & 24 hrs of hypoxia (P<0.001 & P< 0.001, respectively). Hypoxia inducible factor (HIF) 1 α gene was down-regulated after 4, 8 and 24 hours of hypoxia (P=0.036, P=0.011, P=0.018, respectively) as others have previously described. Here, we demonstrate for the first time that ANXA1 gene and its two receptors FPRL1 & FPR1 are expressed in human SGBS adipocytes. Low levels of oxygen inhibit the expression of ANXA1 in the preadipocytes suggesting that AnxA1 may have a role in the regulation of inflammatory and pro-resolution pathways necessary to restore homeostasis in the inflamed adipose tissue. Our study suggests the utility of further investigations into the role of AnxA1 in cellular inflammation. Manipulation of cellular levels of AnxA1 would be of interest to further clarify its relative role in systemic inflammatory status.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: Declaration of Funding: Dr D Renshaw is supported by an Early Career grant from the Society for Endocrinology. A Kosicka-Knox was supported by a 2 year scholarship from the Human and Health Sciences Department, School of Life Sciences, University of Westminster.