Introduction: Obesity results in an imbalance of systemic adipokines as well as pro and anti-inflammatory biomarkers. The attenuation of anti-inflammatory proteins, including Annexin A1 (AnxA1) in human obesity, may be a contributing factor to the chronic inflammatory phenotype which results. However, increased AnxA1 mRNA and protein levels in mature adipocytes suggest an additional role for AnxA1 in adipose tissue biology.
Aims: 1) To investigate the role of AnxA1 in adipogenesis. 2) To investigate the effects of AnxA1 treatment on inflammatory biomarkers in an obese phenotype.
Methods: 1) SGBS preadipocytes were differentiated with or without 10μM FPR2/ALX receptor antagonist; WRW4 for 14 days. Lipid accumulation was assessed by Oil Red O stain, imaged and analysed using Image J. 2) Differentiated SGBS cells were treated with 10 μM Ac 2-26 peptide and incubated in normoxic (21% O2) or hypoxic (1% O2) conditions for 24 hours to achieve obesogenic conditions. Gene expressions were analysed via RT-qPCR and normalised against GAPDH. Statistical analysis was preformed using GraphPad Prism version 5. Statistical significance was determined using T test at 95% level.
Results: 1) Lipid accumulation significantly decreased in adipocytes differentiated with WRW4 compared to control cells (11.42±5.157 SD, 13.92±5.867 SD, P=0.0092 n=6, respectively). However, increased expression of genes regulating lipogenesis (SREB, PPARγ, ACC, FAS and GPAT) were observed in adipocytes treated with WRW4. 2) Treatment with Ac 2-26 peptide significantly decreased adipocyte specific proinflammatory biomarkers; Adipsin (0.325±0.335, P=0.0025, n=4), Resistin (0.139±0.073, P<0.0001, n=4) and Leptin (0.381±0.507, P=0.027, n=4) in obesogenic cell model.
Conclusion: 1) Endogenous AnxA1 may act through FPR1 to decrease lipid accumulation and adipogenesis. 2) The AnxA1/FPR2 receptor pathway could be used as a therapeutic mechanism to dampen obesity induced inflammation.