SRP Diabetes Postdoc Fellowships - Project 5
Project title: Mechanisms linking white adipocyte glutamine metabolism to insulin resistance.
Prinicipal Investigators: Mikael Rydén and Niklas Mejhert
Department of Medicine, Huddinge
Mechanisms linking white adipocyte glutamine metabolism to insulin resistance.
We recently demonstrated that glutamine levels are lower in white adipocytes from obese compared to lean subjects and that this leads to white adipose tissue (WAT) inflammation (Petrus, Lecoutre et al, Cell Metabolism, 2020). Our new preliminary data in human and murine WAT, reveal that these changes are associated with decreased expression of Glutamine Synthase (GS, encoded by GLUL) and increased expression of glutaminase (GLS, encoded by GLS), the two enzymes governing glutamine metabolism. This suggests that glutamine turnover is a major determinant of adipocyte function. To further dissect the pathophysiological role of our observations in vivo, we have generated adipocyte-specific Gls and Glul knockout mice where we will study the effects of different perturbations on WAT and whole body metabolism. These analyses will be complemented by state-of-the-art mechanistic studies in human adipocytes in which we for instance will perform metabolic flux analyses following CRISPR/Cas9-mediated engineering of the glutamine pathway. Our project will allow the applicant to work with an array of methods in clinical translational research and provide unprecedented insights into the immunometabolic role of adipocyte glutamine turnover.
Read the complete project description.
How to apply
The closing date for applications has been brought forward to midnight CEST on Sunday 15th May, 2022.