Fuse your mitochondria, lose appetite: an anorexic, anti‐obesity sphingolipid

Abstract Aberrant production of ceramides, the precursors of complex sphingolipids, is a hallmark of obesity and strongly linked to metabolic dysfunction (Meikle and Summers 2017). Ceramides are formed by recycling or de novo synthesis from sphingosine and a fatty acid side chain moiety. The side ch...

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Bibliographic Details
Main Authors: Carolin Muley, Alexander Bartelt
Format: Article
Language:English
Published: Springer Nature 2021-07-01
Series:EMBO Molecular Medicine
Online Access:https://doi.org/10.15252/emmm.202114618
Description
Summary:Abstract Aberrant production of ceramides, the precursors of complex sphingolipids, is a hallmark of obesity and strongly linked to metabolic dysfunction (Meikle and Summers 2017). Ceramides are formed by recycling or de novo synthesis from sphingosine and a fatty acid side chain moiety. The side chain length determines lipotoxicity of ceramides, as those composed of C16:0 or C18:0 side chains are toxic whereas those with C24:0 or C24:1 are not (Meikle and Summers 2017). Counteracting the deleterious effects of high‐fat diets (HFDs) rich in saturated fat either by inhibiting synthesis or by promoting degradation of ceramides mitigates insulin resistance and ectopic lipid accumulation (Meikle and Summers 2017). However, drugs that safely and selectively target ceramide metabolism have failed to translate into metabolic benefit in human trials so far.
ISSN:1757-4676
1757-4684