Fuse your mitochondria, lose appetite: an anorexic, anti‐obesity sphingolipid. Issue 8 (19th July 2021)

• Record Type: Journal Article
• Authors: Muley, Carolin; Bartelt, Alexander
• Is Part Of: EMBO molecular medicine. Volume 13:Issue 8(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-19
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.15252/emmm.202114618
• Languages: English
• ISSNs: 1757-4676

Abstract

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. Abstract : A. Bartelt and C. Muley discuss the study by Jayashankar, Selwan et al (in this issue of EMBO Mol Med ) that introduces an orally bioavailable synthetic sphingolipid that enhances mitochondrial fusion, leading to reduced food intake, weight loss, and improved metabolic health in obese mice.