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Austrian Central Bank, Anniversary Fund, project number: 1800

AGMO function and ether lipid metabolism in human adipose tissue biology

Project leader:
Sabrina Sailer, PhD
Institute of Biological Chemistry, Biocenter
Medical University of Innsbruck

Approved: 19.12.2018
Grants awarded: 123,000.00 €
Project start: 01.02.2019
Project end: 31.08.2022

Abstract:

Obesity has emerged as one major health problem in industrial countries leading to cardiovascular diseases and insulin resistance. According to the NCD Risk Factor Collaboration the world’s population becomes 1.5 kg heavier each decade. Lipid profiles of human and cell culture samples show that not only ester lipids but also their very poorly characterized ether analogues are accumulating in adipose tissue and adipocytes. Alkylglycerol monooxygenase (AGMO, E.C. 1.14.16.5) is a very labile transmembrane protein and cleaves the ether bond of alkylglycerols and lyso-alkylglycero-phospholipids in a tetrahydrobiopterin dependent manner. The enzymatic reaction was described already very early in 1964, but it took until 2010 to successfully assign the sequence encoding AGMO. Since then our laboratory focused on the characterization of this enzyme in several cellular models. AGMO is expressed and active in a variety of tissues and cell lines including liver, intestine and adipose tissue and the murine RAW264.7 and 3T3-L1 cell lines. 

In collaboration with Priv.-Doz. Dr.rer.nat Christian Ploner (Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck), human adipose tissue samples are used and further process to (i) isolate primary in vivo adipocytes and (ii) human adipose derived stem cells for in vitro differentiation. The aim of this project is to detangle the role of AGMO and post-peroxisomal ether lipid metabolism in human adipose tissue biology and in vitro differentiation of human adipose derived stem cells.