Cellular and Molecular Life Sciences

, Volume 76, Issue 6, pp 1107–1134 | Cite as

The role of dihydrosphingolipids in disease

  • Ruth. R. Magaye
  • Feby Savira
  • Yue Hua
  • Darren J. Kelly
  • Christopher Reid
  • Bernard Flynn
  • Danny Liew
  • Bing H. WangEmail author


Dihydrosphingolipids refer to sphingolipids early in the biosynthetic pathway that do not contain a C4-trans-double bond in the sphingoid backbone: 3-ketosphinganine (3-ketoSph), dihydrosphingosine (dhSph), dihydrosphingosine-1-phosphate (dhS1P) and dihydroceramide (dhCer). Recent advances in research related to sphingolipid biochemistry have shed light on the importance of sphingolipids in terms of cellular signalling in health and disease. However, dihydrosphingolipids have received less attention and research is lacking especially in terms of their molecular mechanisms of action. This is despite studies implicating them in the pathophysiology of disease, for example dhCer in predicting type 2 diabetes in obese individuals, dhS1P in cardiovascular diseases and dhSph in hepato-renal toxicity. This review gives a comprehensive summary of research in the last 10–15 years on the dihydrosphingolipids, 3-ketoSph, dhSph, dhS1P and dhCer, and their relevant roles in different diseases. It also highlights gaps in research that could be of future interest.


Adipocyte Aging Airway hypersensitivity Apoptosis Autophagy Cancer Cardiomyopathy Ceramide Ceramide synthase Dihydroceramide desaturase 1-Des-1 Diabetes Dihydrosphinganine FB1 toxicity Hypoxia Neurodegenerative Sphingosine kinase Serine palmitoyl transferase Sphingosine-1-phosphate—S1P Sphingosine-1-phosphate receptors 4-HRP fenretinide 



3-Ketosphinganine Reductase


N-(4-Hydroxyphenyl) retinamideFenretinide




Alkaline ceramidase 3


Acyl-coenzyme A synthase


Δ20 acyl-coenzyme A synthase lacking exon 20


Adiponectin hormone


American Heart Association


Protein kinase B


AMP activated protein kinase


Body mass index


Coronary artery disease


Cyclic adenosine 3ʹ,5ʹ-monophosphate




Cyclin dependent kinase 2




Ceramide like kinase


Ceramide kinase


Ceramide synthase


Cystic fibrosis transmembrane conductance regulator


Cyclooxygenase 2


Cardiorespiratory fitness


Connective tissue growth factor


Cardiovascular disease


Dihydroceramide desaturase 1


Dihydroceramide desaturase 2






Dihydrosphingosine 1 phosphate/dihydrosphinganine 1 phosphate


Ethanolamine phosphate


Endoplasmic reticulum


Extracellular signal regulated kinases


Focal adhesion kinase


Fumonisin B 1


Free fatty acid


Histone deacetylase 2


High density lipid


Human hepato-carcinoma cell


Hypoxia inducible factor 1-α


Homestasis model of insulin resistance


Heat shock protein 27


Human umblical endothelial cell




Interleukin 1


Interleukin 6


c-Jun N terminal kinase


Low density lipid




Lipidomic risk score


Mitogen activated protein kinases


Myocardial infarct


Manganese(III) tetrakis (4-benzoic acid) porphyrin


Mammalian target of rapamycin complex 1


Nicotinamide adenine nucleotide


Nicotinamide adenine nucleotide phosphate


Non-alcoholic fatty liver disease


Nuclear factor of activated T cells


Nuclear factor kappa light chain enhancer of B cell


Nuclear factor erythroid related factor 2


Platelet derived growth factor


Photodynamic therapy


Phosphorylated eukaryotic translation initiation factors 2α


PKR like endoplasmic reticulum kinase


Protein kinase Cα


Phospholipase D


Peroxisome proliferator-activated receptor γ


Retinoic acid receptor


Renal mesengial cell


Reactive oxygen species


Ribosomal protein S6 kinase


San Antonio Family Heart Study


Dual specificity mitogen activated protein kinase kinase 1


Sprague Dawley

SK 1 and 2

Sphingosine kinase 1 and 2


Sphingosine 1 phosphate


Sphingosine 1 phosphate phophatase


Sphingosine 1 phosphate receptor 1–5


Sphingosine 1 phosphate lyase


Serine palmitoyltransferase


Serine palmitoyltransferase long chain base 1


Serine palmitoyltransferase long chain base 3


ST-segment elevation myocardial: infarct


Squamous cell carcinoma cell


Type 2 diabetes mellitus


Tumour necrosis factor α


Vascular endothelial growth factor


Waist circumference


Author contributions

RM and BW conceived and designed review question, conducted preliminary data search, and sorting the papers. FS and YH conducted literature search and screening. DK, CR, BF and DL assisted drafting and edited of the paper and had responsibility for its final content. All authors read and approved the final manuscript.


This research was supported by National Health and Medical Research Council of Australia Program Grants (1092642) (BHW, DL, CR and DJK) and Project Grant (1087355) (BHW). RM and FS are sponsored by a Monash Graduate Scholarship and Monash International Postgraduate Research Scholarship for their doctoral studies.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Ruth. R. Magaye
    • 1
  • Feby Savira
    • 1
  • Yue Hua
    • 1
  • Darren J. Kelly
    • 2
  • Christopher Reid
    • 1
  • Bernard Flynn
    • 3
  • Danny Liew
    • 1
  • Bing H. Wang
    • 1
    Email author
  1. 1.Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
  2. 2.Department of Medicine, St Vincent’s HospitalUniversity of MelbourneFitzroyAustralia
  3. 3.Australian Translational Medicinal Chemistry Facility, Medicinal Chemistry, Monash Institute of Pharmaceutical SciencesMonash UniversityMelbourneAustralia

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