Abstract 6258: Increased HO-1 Expression Decreases Adipocyte Cell Size, IL6 And TNFα Secretion While Increasing Adiponectin Levels In Obese Zucker Rats And Human Adipocyte Stem Cells
Background. Adiponectin has been shown to provide cytoprotection to both the pancreatic and vascular systems. Our hypothesis is that upregulation of HO-1 expression influences serum adiponectin and ameliorates the levels of inflammatory cytokines in obese Zucker fat (ZF) rats and Zucker lean (ZL) rats via an increase in adiponectin levels and inhibition of adipogenesis in vivo and in adipocyte stem cells.
Methods. ZF and ZL rats were fed a normal diet until 12–14 weeks of age when they were divided into four groups comprising ZL, ZL-CoPP, ZF and ZF-CoPP. CoPP (subcutaneously, 2mg/Kg weekly) was administered for 6 weeks. Food intake, blood insulin, glucose levels, aorta HO-1, pAMPK, AKT, pAKT protein and O−2 were determined. Human bone marrow derived adipocyte mesenchymal stem cells (MSC) were used to measure the effect of HO-1 expression on adipogenesis and droplet size. Plasma adiponectin, TNFα and IL-6 were measured.
Results. CoPP administration limited weight gain and increased both HO-1 expression and plasma adiponectin (p<0.004). This was associated with a decrease in superoxide levels (p<0.05) when compared to untreated ZF rats. CoPP treatment decreased visceral and subcutaneous fat content and reduced weight gain (p<0.01). TNFα and IL-6 were also decreased (p<0.04 and 0.008 respectively). Human bone marrow-derived adipocytes cultured with CoPP resulted in an increase in HO-1 protein levels and a decrease in superoxide levels. Upregulation of HO-1 caused adipose remodeling, (decreased lipid droplets by 52% while inhibition of HO activity increased lipid droplet size by 128%) and increased adiponectin secretion in the culture medium of human bone marrow-derived adipocytes.
Conclusion. This study demonstrates that the anti-obesity effects of HO-1 induction result in an increase in adiponectin secretion, both in vivo and in vitro, a decrease in TNFα, IL-6, a reduction in weight gain and decreased adipocyte size resulting in a healthier adipocyte as seen by an increase in adiponectin. This highlights the pivotal role and symbiotic relationship of HO-1 and adiponectin in the modulation of the metabolic syndrome phenotype.