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Journal of Inherited Metabolic Disease
Published in: Journal of Inherited Metabolic Disease 1/2015

01-01-2015 | Complex Lipids

Inborn errors of cytoplasmic triglyceride metabolism

Authors: Jiang Wei Wu, Hao Yang, Shu Pei Wang, Krishnakant G. Soni, Catherine Brunel-Guitton, Grant A. Mitchell

Published in: Journal of Inherited Metabolic Disease | Issue 1/2015

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Abstract

Triglyceride (TG) synthesis, storage, and degradation together constitute cytoplasmic TG metabolism (CTGM). CTGM is mostly studied in adipocytes, where starting from glycerol-3-phosphate and fatty acyl (FA)-coenzyme A (CoA), TGs are synthesized then stored in cytoplasmic lipid droplets. TG hydrolysis proceeds sequentially, producing FAs and glycerol. Several reactions of CTGM can be catalyzed by more than one enzyme, creating great potential for complex tissue-specific physiology. In adipose tissue, CTGM provides FA as a systemic energy source during fasting and is related to obesity. Inborn errors and mouse models have demonstrated the importance of CTGM for non-adipose tissues, including skeletal muscle, myocardium and liver, because steatosis and dysfunction can occur. We discuss known inborn errors of CTGM, including deficiencies of: AGPAT2 (a form of generalized lipodystrophy), LPIN1 (childhood rhabdomyolysis), LPIN2 (an inflammatory condition, Majeed syndrome, described elsewhere in this issue), DGAT1 (protein loosing enteropathy), perilipin 1 (partial lipodystrophy), CGI-58 (gene ABHD5, neutral lipid storage disease (NLSD) with ichthyosis and “Jordan’s anomaly” of vacuolated polymorphonuclear leukocytes), adipose triglyceride lipase (ATGL, gene PNPLA2, NLSD with myopathy, cardiomyopathy and Jordan’s anomaly), hormone-sensitive lipase (HSL, gene LIPE, hypertriglyceridemia, and insulin resistance). Two inborn errors of glycerol metabolism are known: glycerol kinase (GK, causing pseudohypertriglyceridemia) and glycerol-3-phosphate dehydrogenase (GPD1, childhood hepatic steatosis). Mouse models often resemble human phenotypes but may diverge markedly. Inborn errors have been described for less than one-third of CTGM enzymes, and new phenotypes may yet be identified.
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Metadata
Title
Inborn errors of cytoplasmic triglyceride metabolism
Authors
Jiang Wei Wu
Hao Yang
Shu Pei Wang
Krishnakant G. Soni
Catherine Brunel-Guitton
Grant A. Mitchell
Publication date
01-01-2015
Publisher
Springer Netherlands
Published in
Journal of Inherited Metabolic Disease / Issue 1/2015
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI
https://doi.org/10.1007/s10545-014-9767-7

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