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Title: Lipid droplets in Drosophila models of kidney disease
Author: Lubojemska, Aleksandra
ISNI:       0000 0004 8500 005X
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2019
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The accumulation of lipid droplets (LDs) in ectopic sites is one of the hallmarks of disrupted lipid homeostasis. Adverse effects associated with LD accumulation have been described in many organs, including the kidney. Renal LDs are observed in the context of several pathologies, including diabetic nephropathy and chronic kidney disease. Although the correlation between LDs and compromised renal function is well documented, a causal link has yet to be demonstrated. I have investigated this link using a genetic model, the fruit fly Drosophila melanogaster. I established three new dietary models (low protein, high sugar and high fat) and one genetic "lipid overflow" model (Lpp > ATGL) that strongly increase renal triglyceride accumulation in the LDs of larval pericardial nephrocytes. These "lipotoxicity" models showed that nutritional imbalance, in particular a high fat diet, recapitulates some of the morphological and functional abnormalities observed in human diabetic nephropathy or chronic kidney disease. I then dissected the mechanistic links, on a high fat diet, between genes involved in triglyceride metabolism and the compromised function of nephrocytes in macromolecule endocytosis. This revealed that a high fat diet triggers renal stress via a decrease in the expression of adipocyte triglyceride lipase (ATGL). Boosting ATGL expression is sufficient to rescue high-fat dietary abnormalities in mitochondria and other organelles and, importantly, also to rescue nephrocyte endocytosis. Together, these findings reveal that the flux of fatty acids through LDs is protective for renal function.
Supervisor: Bateman, Joseph Matthew Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available