This model of diet-induced renal lipotoxicity uses animals on a high-fat diet (HFD) throughout larval development. The impact of the HFD on the development and function of adult nephrocytes (podocyte-like cells) has been assessed. A high-fat diet drives nephrocyte lipid uptake leading to the ectopic accumulation of lipid droplets; this process was shown to occur via the multiligand receptor Cubilin (Cubn). The accumulation of nephrocyte lipid droplets correlates with endoplasmic reticulum (ER) and mitochondrial deficits, and with impaired macromolecular endocytosis. Overexpression of adipose triglyceride lipase (ATGL/bmm) rescues the HFD-induced defects in renal endocytosis.
See the human disease model report 'kidney disease (fly models overview)' (FBhh0000738) for information on the fly renal system. See also the related human disease model report 'kidney disease (postulated), CUBN-related' (FBhh0000550).
[updated Jun. 2021 by FlyBase; FBrf0222196]
Chronic kidney disease (CKD) represents the ninth most common cause of death in the United States. Altered renal lipid metabolism, first described in 1982, has been recognized as a common pathway in clinical and experimental CKD of both metabolic and nonmetabolic origin (Kim et al., 2021; https://kidney360.asnjournals.org/content/2/4/755).
One hallmark of kidney disease lipotoxicity is the accumulation of lipid droplets in podocytes and in proximal tubule epithelial cells (FBrf0248980 and references cited therein).
