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J Biol Chem. 2017 Mar 3;292(9):3929-3939. doi: 10.1074/jbc.M116.756460. Epub 2017 Jan 18.

De Novo Sphingolipid Biosynthesis Is Required for Adipocyte Survival and Metabolic Homeostasis.

Author information

1
From the Genetics of Development and Disease Branch and.
2
Mouse Metabolism Core Laboratory, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 and.
3
the Department of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20184.
4
From the Genetics of Development and Disease Branch and proia@nih.gov.

Abstract

Sphingolipids are a diverse class of essential cellular lipids that function as structural membrane components and as signaling molecules. Cells acquire sphingolipids by both de novo biosynthesis and recycling of exogenous sphingolipids. The individual importance of these pathways for the generation of essential sphingolipids in differentiated cells is not well understood. To investigate the requirement for de novo sphingolipid biosynthesis in adipocytes, a cell type with highly regulated lipid metabolism, we generated mice with an adipocyte-specific deletion of Sptlc1 Sptlc1 is an obligate subunit of serine palmitoyltransferase, the enzyme responsible for the first and rate-limiting step of de novo sphingolipid biosynthesis. These mice, which initially developed adipose tissue, exhibited a striking age-dependent loss of adipose tissue accompanied by evidence of adipocyte death, increased macrophage infiltration, and tissue fibrosis. Adipocyte differentiation was not affected by the Sptlc1 deletion. The mice also had elevated fasting blood glucose, fatty liver, and insulin resistance. Collectively, these data indicate that de novo sphingolipid biosynthesis is required for adipocyte cell viability and normal metabolic function and that reduced de novo sphingolipid biosynthesis within adipocytes is associated with adipocyte death, adipose tissue remodeling, and metabolic dysfunction.

KEYWORDS:

adipocyte; inflammation; lipodystrophy; serine palmitoyltransferase; sphingolipid

PMID:
28100772
PMCID:
PMC5339773
DOI:
10.1074/jbc.M116.756460
[Indexed for MEDLINE]
Free PMC Article

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