Keywords: Biology, Models, Methods, Metabolism
Motivation: NMR-based analyses of lipids can reveal the sources and pathways contributing to lipid biosynthesis in cells grown in the presence of 13C-labeled tracers.
Goal(s): Our goal was to determine whether treatment of FLCN-deficient renal cell carcinoma (RCC) cells with the Complex I inhibitor metformin modulated cellular biosynthesis of lipids.
Approach: We utilized 1H-13C HSQC NMR analysis of cellular lipids in FLCN-deficient tumor cells to assess incorporation of acetyl groups derived 13C6-glucose or 13C515N2-L-glutamine into cellular lipids during treatment with metformin.
Results: We observed a sharp decrease in incorporation of 13C-glucose-derived carbon into lipid acyl chains and cholesterol methyl groups following metformin treatment.
Impact: We found that metformin decreased synthesis of lipids from glucose while enhancing lipid synthesis from glutamine in renal tumor cells. These findings demonstrate that targeting Complex I may be a promising therapeutic avenue for treatment and prevention of FLCN-deficient RCC.
How to access this content:
For one year after publication, abstracts and videos are only open to registrants of this annual meeting. Registrants should use their existing login information. Non-registrant access can be purchased via the ISMRM E-Library.
After one year, current ISMRM & ISMRT members get free access to both the abstracts and videos. Non-members and non-registrants must purchase access via the ISMRM E-Library.
After two years, the meeting proceedings (abstracts) are opened to the public and require no login information. Videos remain behind password for access by members, registrants and E-Library customers.
Keywords