ArticleEMBO molecular medicine2021
Drug-like sphingolipid SH-BC-893 opposes ceramide-induced mitochondrial fission and corrects diet-induced obesity.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 27 citations in OpenAlex.
- The Potential Target Value of ADP-Ribosylation Factor 6 in Insulin Secretion Regulation and the Treatment of Metabolic Disorders.Metabolites · 2026Review
- Inhibition of ceramide synthesis ameliorates body wasting in a cancer cachexia model.The Journal of clinical investigation · 2026Article
- Endolysosomal trafficking regulator SH-BC-893 inhibits coronavirus entry in vitro and in vivo.Scientific reports · 2026Article
- Therapeutic remodeling of the ceramide backbone prevents kidney injury.Cell metabolism · 2026Article
- Mitochondrial medicine in obesity: a scoping review.Open medicine (Warsaw, Poland) · 2026Review
- Integrated serum metabolomics reveal molecular mechanism of Xietu Hemu prescription on metabolic dysfunction-associated steatotic liver disease-related obesity.World journal of hepatology · 2025Article
- Impact of Nutrition on Sphingolipid-Regulated Physiology: A Review.Molecular nutrition & food research · 2025Review
- The Gut Microbiome in Human Obesity: A Comprehensive Review.Biomedicines · 2025Review
- Sphingosine simultaneously inhibits nuclear import and activates PP2A by binding importins and PPP2R1A.The EMBO journal · 2025Article
- Cross-regulation between adipose tissue innervation and metaflammation: a potential therapeutic target for obesity.American journal of translational research · 2025Review
- Opaganib Promotes Weight Loss and Suppresses High-Fat Diet-Induced Obesity and Glucose Intolerance.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- The Hydrophilic Metabolite UMP Alleviates Obesity Traits through a HIF2α-ACER2-Ceramide Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mitochondrial Dysfunction and Metabolic Reprogramming in Obesity and Asthma.International journal of molecular sciences · 2024Review
- STZ-induced hyperglycemia differentially influences mitochondrial distribution and morphology in the habenulointerpeduncular circuit.Frontiers in cellular neuroscience · 2024Article
- CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.Nature communications · 2023Article
- Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics.Nucleic acids research · 2023Article
- Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes.Metabolites · 2023Review
- Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis.Nature cell biology · 2023Article
- Liraglutide Counteracts Endoplasmic Reticulum Stress in Palmitate-Treated Hypothalamic Neurons without Restoring Mitochondrial Homeostasis.International journal of molecular sciences · 2022Article
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15 authors at 3 institutions in 3 countries.
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Abstract
Ceramide-induced mitochondrial fission drives high-fat diet (HFD)-induced obesity. However, molecules targeting mitochondrial dynamics have shown limited benefits in murine obesity models. Here, we reveal that these compounds are either unable to block ceramide-induced mitochondrial fission or require extended incubation periods to be effective. In contrast, targeting endolysosomal trafficking events important for mitochondrial fission rapidly and robustly prevented ceramide-induced disruptions in mitochondrial form and function. By simultaneously inhibiting ARF6- and PIKfyve-dependent trafficking events, the synthetic sphingolipid SH-BC-893 blocked palmitate- and ceramide-induced mitochondrial fission, preserved mitochondrial function, and prevented ER stress in vitro. Similar benefits were observed in the tissues of HFD-fed mice. Within 4 h of oral administration, SH-BC-893 normalized mitochondrial morphology in the livers and brains of HFD-fed mice, improved mitochondrial function in white adipose tissue, and corrected aberrant plasma leptin and adiponectin levels. As an interventional agent, SH-BC-893 restored normal body weight, glucose disposal, and hepatic lipid levels in mice consuming a HFD. In sum, the sphingolipid analog SH-BC-893 robustly and acutely blocks ceramide-induced mitochondrial dysfunction, correcting diet-induced obesity and its metabolic sequelae.
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