Presentation description

A sphingolipid derivative, ceramide, has been associated with the development of type 2 diabetes and other metabolic diseases. A recent diversity-outbred panel of mice revealed new genetic characters that may play a role in this story. This family of genes has relatively unknown mechanisms but is predicted to act in lipid metabolism. Previous research found that metabolically diseased animal and human models also displayed mutations or polymorphisms of these genes. We suspect that a specific gene in this family may catalyze the reaction that produces acyl-CoA from fatty acid chains and coenzyme A. The acyl-CoA produced could end up in storage, produce ceramides and other complex lipids, or feed into beta oxidation. To characterize the function of this gene, a transgenic mouse line was developed to knock out its expression in the liver. This study aims to assess how this manipulation affects lipid accumulation and metabolic load. This study revealed that deletion of this gene in the liver decreased hepatic ceramides and increased glucose tolerance. A notable difference was observed selectively among female mice. The current results of the study suggest that this gene has a similar function to other members of its family. To further characterize this gene's function, future analyses will explore its protein expression and histological effects. Additional studies will assess its function through a whole-body knockout model, an overexpression in vivo model, and a kidney-specific model. Together, these studies have the clinical potential to aid targeted interventions for metabolic disease.