Sphingolipids and hepatic steatosis.

Abstract

The development of a fatty liver predisposes individuals to an array of health problems including diabetes, cardiovascular disease and certain forms of cancer. Inhibition or genetic ablation of genes controlling sphingolipid synthesis in rodents resolves hepatic steatosis and in many cases wards off the health complications associated with excessive hepatic triglyceride accumulation. Examples include the pharmacological inhibition of serine palmitoyltransferase or glucosylceramide synthase or the genetic depletion of acid sphingomyelinase, which dramatically reduce hepatic triglyceride levels in mice susceptible to the development of a fatty liver. The magnitude of the effects on triglyceride depletion in these models is impressive, but the relevance to humans and the mechanism of action is unclear. Herein we probe into the connections between sphingolipids and triglyceride synthesis in an attempt to identify causal relationships and opportunities for therapeutic intervention.

• Authors: Benjamin T Bikman, Scott A Summers
• Journal: Advances in experimental medicine and biology (Adv Exp Med Biol) Vol. 721 Pg. 87-97 ( 2011) ISSN: 0065-2598 [Print] United States
• PMID: 21910084 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Adiponectin
• Cytokines
• Fatty Acids
• Sphingolipids
• Triglycerides
• Serine C-Palmitoyltransferase
• Glucosyltransferases
• ceramide glucosyltransferase
• Sphingomyelin Phosphodiesterase

Topics

• Adiponectin (physiology, therapeutic use)
• Animals
• Cardiovascular Diseases (metabolism)
• Cytokines (physiology)
• Diabetes Mellitus, Type 2 (metabolism)
• Disease Models, Animal
• Fatty Acids (metabolism)
• Fatty Liver (genetics, metabolism)
• Glucosyltransferases (antagonists & inhibitors, metabolism)
• Humans
• Inflammation (metabolism)
• Liver (metabolism)
• Metabolic Syndrome (genetics, metabolism)
• Mice
• Neoplasms (metabolism)
• Non-alcoholic Fatty Liver Disease
• Obesity (metabolism)
• Serine C-Palmitoyltransferase (antagonists & inhibitors, physiology)
• Sphingolipids (metabolism)
• Sphingomyelin Phosphodiesterase (deficiency, genetics, physiology)
• Triglycerides (metabolism)