Endocrine Abstracts

Introduction: Adipose tissue oxygen consumption and blood flow are altered in obesity inducing local tissue hypoxia. Hypoxia affects several biological functions including adipogenesis, inflammation, insulin resistance and metabolism affecting the overall degree of adiposity. The expression of Annexin A1 (ANXA1); an anti-inflammatory protein, increases in the adipose tissue in response to obesity and further increases in the subcutaneous adipose tissue of old obese individuals compared to young obese individuals however, the roles of ANXA1 in the adipose tissue or obesity are unclear.

Aim: The aim of this study was to investigate the potential roles of ANXA1 in adipocytes using an in vitro model of obesity.

Methods: Differentiated SGBS cells were treated with and without 10 μM AC2-26 peptide and incubated in hypoxia (1% O₂) 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: AC2-26 treatment differentially regulated the expression of genes involved in the insulin signalling pathway, adipocytokine signalling pathway, PPAR signalling pathway, metabolism and inflammation. SREBF1 (P=0.0253, n=3), FASN (P=0.0125, n=3), SLC2A4 (P=0.0278, n=3) and IRS1 (P<0.0001, n=3), TNF (P=0.0429, n=3), LEP (P=0.0400, n=3), NAMPT (P=0.0039, n=3), RETN (P<0.0001, n=4), ACOX1 (P=0.030, n=3), DPP4 (P=0.0170, n=3), IGFR1 (0.0394, n=3) and CD36 (P=0.0305, n=3) were significantly downregulated. ADIPOQ (P=0.0073, n=3), PPARA (P=0.0303, n=3) and IL-6 (P=0.0072, n=3) were significantly upregulated.

Summary: The regulation of genes in response to acute AC2-26 indicate a protective role of ANXA1 in obesity and inflammation and provide a novel strategy to prevent the development of obesity associated inflammation and metabolic diseases. The results of this study further indicate an insulin sensitising role of ANXA1.