Date of this Version
Schaecher, Cameron et al. Identification of Sestrin2 Regulated Metabolites and Adipocytokines in 3T3-L1 Mouse White Adipocytes. University of Nebraska-Lincoln. 2018.
White adipose tissue (WAT) secretes adipocytokines and lipid metabolites to protect surrounding organs in order to protect the human body under various energy stress conditions (e.g. starvation or high fructose diet). Mammalian Sestrin2 can be induced under energy stress conditions and induce autophagy process, which is the self-eating process for damaged proteins and organelles in the cytosol, by inhibiting mechanistic target of rapamycin complex 1 (mTORC1). Upon mTORC1 inhibition, mTORC1 downstream Unc51-like autophagy activating kinase 1 (ULK1, aka ATG1) can be activated and phosphorylate Sestrin2 in order to initiate autophagy processes. The various levels of autophagy induction according to each stress conditions are correlated with Sestrin2 phosphorylation levels and would affect adipocyte metabolism and its adipocytokine secretion into the blood stream. However, there is unknown connection between Sestrin2 induction level and adipocyte differentiation and function. The focus of this project is to determine how different level of Sestrin2 in white adipocytes affect secretion of lipid metabolites and adipocytokines, which are prominent indicators of adipocyte stress adaptations. Through adipocytes cell culture and following metabolomics analysis and adipocytokine assay in both cell lysate and surrounding growth media, we found that both adipocyte functions can be uniquely regulated by Sestrin2 induction levels. The outcome of this project will lead to Sestrin2 phosphorylation mimetic drugs or lipid metabolism targeting drugs, which can be protective against obesity-associated diseases such as diabetes and cancer in humans.