- Lysosomal stress: a new player in perturbed lipid metabolism
M.C. van Eijk
- Award date
- 4 April 2017
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Lysosomes are involved in many different essential cellular processes, among others organelle and molecule degradation, exocytosis, cell energy metabolism, cholesterol and sphingolipid level regulation. Lysosomal stress has a strong impact on the immune system, affecting specially macrophages as these cells greatly relay on their endolysosomal activity for their function. In lysosomal storage diseases (LSDs) such as Gaucher dieasease (GD) and Niemann Pick-C (NPC) , macrophages present a unique phenotype with accumulation of non-hydrolyzed lipids as driver of their phenotype.
The first aim of this thesis is the search for a novel marker that reflects the lysosomal lipid accumulation phenotype as found in LSD and obesity. The second aim is to analyze if specific lipids in obese adipose tissue macrophages contribute to their function/phenotype. Finally, it is addressed if glycosphingolipids (GSL) manipulation in adipose tissue of lean mice impacts iNKT cell function.
- Please note that—for copyright reasons—chapter 5 (pp. 111-126) is not included in the thesis download.
Chapter 4: HEPES promotes a MIT/TFE-mediated lysosomal-autophagic gene network in cultured cells: A call for caution (Embargo up to and including 4 April 2019)
Chapter 6: Induction of Sphk1 activity in obese adipose tissue macrophages promotes survival (Embargo up to and including 4 April 2019)
Chapter 7: Endogenous adipocyte-derived glucosylceramides drive iNKT cell function (Embargo up to and including 4 April 2019)
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