Open AccessFuse your mitochondria, lose appetite: an anorexic, anti‐obesity sphingolipid
Author(s) -
Muley Carolin,
Bartelt Alexander
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202114618
Subject(s) - sphingolipid , ceramide , lipotoxicity , sphingosine , insulin resistance , autophagy , endocrinology , lipid metabolism , chemistry , medicine , mitochondrion , biochemistry , microbiology and biotechnology , biology , insulin , apoptosis , receptor
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.