Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 2; p. 187
• Main Authors: Missaglia, Sara, Coleman, Rosalind A, Mordente, Alvaro, Tavian, Daniela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.02.2019; MDPI
• Subjects: 1-Acylglycerol-3-Phosphate O-Acyltransferase - chemistry; 1-Acylglycerol-3-Phosphate O-Acyltransferase - metabolism; ABHD5; Adipocytes; Animals; Biosynthesis; Cardiac muscle; cardiomyopathy; Cardiovascular disease; Cell culture; Diabetes; Energy balance; Energy metabolism; Esters; Fibroblasts; Gene expression; Homeostasis; Humans; Hydrolase; Ichthyosis; induced pluripotent stem cells; Insulin resistance; Jordans’ anomaly; lipid droplet; Lipid Droplets - metabolism; Lipid Droplets - ultrastructure; Lipid metabolism; Lipid Metabolism, Inborn Errors - metabolism; Lipids; liver steatosis; Mammals; Metabolism; Models, Biological; Muscles - pathology; Muscles - ultrastructure; Mutation; Myopathy; NLSD; Organelles; PNPLA2; Proteins; Review; Storage diseases; Structure-function relationships; Vitamin A; lipid droplet; fibroblasts; myopathy; lipid metabolism; liver steatosis; Jordans’ anomaly; induced pluripotent stem cells; ABHD5; NLSD; cardiomyopathy; ichthyosis; PNPLA2
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8020187

Neutral lipid storage disease with myopathy (NLSDM) and with ichthyosis (NLSDI) are rare autosomal recessive disorders caused by mutations in the and in the genes, respectively. These genes encode the adipose triglyceride lipase (ATGL) and α-β hydrolase domain 5 (ABHD5) proteins, which play key roles in the function of lipid droplets (LDs). LDs, the main cellular storage sites of triacylglycerols and sterol esters, are highly dynamic organelles. Indeed, LDs are critical for both lipid metabolism and energy homeostasis. Partial or total or knockdown is characteristic of the cells of NLSD patients; thus, these cells are natural models with which one can unravel LD function. In this review we firstly summarize genetic and clinical data collected from NLSD patients, focusing particularly on muscle, skin, heart, and liver damage due to impaired LD function. Then, we discuss how NLSD cells were used to investigate and expand the current structural and functional knowledge of LDs.