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Sphingolipids and insulin resistance: the five Ws
1Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore. scott.summers@duke-nus.edu.sg
Current Opinion in Lipidology
|March 11, 2010
Summary
Inhibiting sphingolipid synthesis improves insulin sensitivity and prevents diabetes by targeting ceramides and glucosylceramides. Further research is needed to fully understand their roles in metabolic disease.
Area of Science:
- Metabolic disease research
- Endocrinology
- Lipid metabolism
Background:
- Sphingolipid synthesis inhibition improves insulin sensitivity, resolves hepatic steatosis, and prevents diabetes in obese rodents.
- Understanding the roles of sphingolipids in diabetes pathogenesis is crucial.
Purpose of the Study:
- To review interventional studies on sphingolipid synthesis inhibition.
- To address the 'Who, What, Where, When, and Why' of sphingolipids in diabetes pathogenesis.
Main Methods:
- Review of interventional studies on sphingolipid synthesis.
- Analysis of roles of ceramides and glucosylceramides in insulin action.
- Investigation of tissue-specific effects and inflammation's role.
Main Results:
- Ceramides and glucosylceramides act as independent antagonists of insulin action.
- Ceramides may inhibit insulin action in skeletal muscle; glucosylceramides in adipose tissue.
- Obesity-induced inflammation is important for sphingolipid synthesis.
Conclusions:
- Significant knowledge gaps exist regarding how sphingolipids induce metabolic disease.
- Elucidating molecular details is essential for developing new therapeutic strategies.
- Targeting sphingolipid action may ameliorate metabolic diseases.
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