Endocrine Abstracts

Previous studies demonstrated that the N-terminal peptide of annexin A1 (AnxA1) (peptide Ac2-26) can mimic the anti-inflammatory actions of the full-length protein in various systems. In the current study, we report the effectiveness of the peptide Ac2-26 as an anti-inflammatory agent in a model of human SGBS adipocytes. We have previously demonstrated that plasma AnxA1 protein is significantly inversely correlated with BMI, body fat level and waist to hip ratio. We have also shown that ANXA1 gene is expressed in human SGBS adipocytes and hypoxia reduces the expression of ANXA1 gene showing that AnxA1 may act as a counter regulator of adipose tissue inflammation. Given that low-level systemic inflammation is seen in metabolic syndrome-associated chronic pathologies, here, we investigate if Ac2-26 peptide can have an effect on the inflammatory markers in human SGBS cells. To mimic the relative hypoxia found in the white adipose tissue of obese humans, mature adipocytes (14 days post-confluent) were treated with 4, 8 and 24 h hypoxia treatment (1% O₂). The cells were also treated with 10-5 M Ac2-26 peptide or vehicle (DMEM/F12 medium supplemented with insulin (20 nM). Cells were collected and SYBR green PCR analysis performed for CRP, IL-6, adiponectin and leptin genes which have been all shown previously to be altered by hypoxia (1% O₂) in SGBS cells. We found that CRP expression was significantly down-regulated following 4, 8 and 24 h of hypoxia treatment in the cells also treated with Ac2-26 peptide compared to vehicle alone (P=0.027, P=0.042 and P=0.014, respectively). IL-6 was also found to be significantly down-regulated after 24 h hypoxia treatment in the Ac2-26 treated cells compared to vehicle (P=0.013). There was no significant difference in the expression of adiponectin, or leptin at any of the time points measured with either Ac2-26 treated cells or vehicle controls.

Here, we demonstrate for the first time that an AnxA1 mimetic, Ac2-26 peptide, regulates pro-inflammatory markers in human SGBS adipocytes. These data show the effectiveness of the peptide Ac2-26 as an anti-inflammatory therapeutic agent in a human SGBS adipocyte model. Furthermore, AnxA1 may be an important modulator of inflammatory and pro-resolution pathways necessary to restore homeostasis in the inflamed adipose tissue of the obese.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however, funding details unavailable.