gms | German Medical Science

Introduction: Obesity is one of the most serious health problems of the 21st century. It is associated with highly increased risk of type 2 diabetes, high blood pressure, cardiovascular disease as well as several cancers. Bariatric surgery like gastric band, gastric bypass or sleeve gastrectomy significantly reduces bodyweight and fat tissue as well as the risk of specific obesity co-morbidities. This is due to the fact that bariatric operation induces changes in the concentration of certain adipokines. Important adipokines are the vascular endothelial growth factor (VEGF) and Apelin-12. VEGF is produced in large quantities by preadipocytes. It is required for angiogenesis in expanding fat tissue. An increase of this peptide hormone seems to be strongly connected to obesity. In addition, VEGF stimulates tumor associated angiogenesis. Apelin-12, another important adipokine has an inhibiting effect on adipogenesis. It is able to reduce the mass of white fat tissue and could be an opponent of VEGF.

The purpose of this study is to investigate whether bariatric surgery directly influences concentrations of VEGF and Apelin-12 in the serum of obese patients. Moreover it will be analyzed whether both hormones correlate with the BMI of the patients. We will answer the question whether serum concentrations of VEGF and Apelin-12 are appropriate parameters to evaluate the success of bariatric surgery.

Another part of the study is to elucidate how Apelin-12 is affecting differentiation of adipocytes focusing on the regulatory CHOP protein, which inhibits adipocyte differentiation. Its increase leads to reduced formation of fat droplets as well as delayed activity of C/EBPβ and PPARγ. The intracellular concentrations of CHOP and PPARγ in LiSA-2 cell preadipocytes and their changes in response to Apelin-12 were studied.

Material and methods: Twenty four patients underwent gastrectomy, gastric band- or gastric bypass surgery and were involved in the study. Blood samples were obtained before and 6 months after surgery. Quantification of the adipokine concentrations was carried out by use of the ELISA-technique. For VEGF the sandwich enzyme immunoassay technique was used, while for apelin-12 the competitive inhibition enzyme technique was applied. In both cases the original serum was used. In-vitro-adipogenesis was induced in LiSa-2 cells, a cell model for adipocyte differentiation, in the presence of Apelin-12. After different stages of adipogenesis CHOP protein and PPARγ were estimated in the cell lysate of the incubated LiSa-2 cells using SDS-PAGE and Western blot. Adipogenesis was visualized by colouring the adipocytes’ fat droplets with Oil-Red O.

Results: It was found that after surgery serum VEGF concentrations significantly decreased, while serum concentrations of Apelin-12 significantly increased. VEGF positively correlated with the BMI, whereas Apelin-12 had a negative correlation with the BMI of patients. In-vitro-adipogenesis in the presence of Apelin-12 showed an increase of CHOP while PPARγ decreased.

Conclusion: Circulating concentrations of VEGF and Apelin-12 are useful to evaluate the success of bariatric surgery. Apelin-12 could possibly have a lasting effect in obese patients after surgery since it reduces fat tissue formation by blocking adipogenesis.