2024-03-042024-03-042018-05https://hdl.handle.net/2346/97692Obesity is one of the key factors in health related issues of our times and prevalence of obesity has nearly tripled since 1975. Angiogenesis is the process of blood vessel formation from endothelial cells or pre-existing vessels and closely associated with obesity or adipose tissue formation. So controlling angiogenesis can be a modulating factor for obesity. Methionine Amino Peptidase 2 (MetAP2) a metalloproteinase, has been shown be a regulatory element for angiogenesis and a target molecule for anti-angiogenic compounds. In our study we have investigated the effect of a MetAP2 inhibitor compound BL6 on adipogenesis. Our central hypothesis is that MetAP2 inhibitor BL6 will block adipogenesis in murine 3T3-L1 cells by blocking angiogenesis. Angiogenesis is also associated with tube formation of Human Umbilical Vein Endothelial Cells (HUVEC). Therefore, we also hypothesized that compound BL6 will also inhibit tube formation in HUVECs. Murine 3T3-L1 cells were treated with MetAP2 inhibitor compound BL6 (20µM, 50 µM and100µM) during differentiation with MDI cocktail. Cells were differentiated for 8 days followed by staining with Oil Red O to determine lipid accumulation. Protein and RNA was also extracted from these cells. Adiponectin, PPARγ, C/EBPα, C/EBP Beta, SREBP1 and FAS expression was quantified by Western Blot and RT-PCR. During in vitro differentiation of mouse 3T3-L1 preadipocytes, administration of 50μM and 100µM of BL6 resulted in reduced lipid accumulation (P<0.05). 100µM BL6 also resulted in decreased Adiponectin, PPAR γ, SREBP1 and FAS level though not significant. Surprisingly, elevated level of C/EBPα was observed inspite block to PPAR γ. Furthermore, cells treated with BL6 during the differentiation period maintained normal metabolic health and improved glucose uptake despite suppression of adipogenesis. Apart from block to adipogenesis, tube formation reduction in HUVECs was observed when administered with 20μM and 50μM of BL6. Collectively this proof of concept study supports the development of a MetAP2 inhibitor, BL6 as a putative therapeutic agent.Application/pdfenAdipogenesisAngiogenesisMetAP2 InhibitionObesity TreatmentThesisRestricted until 03/2023.