Exploring The Role Of Atp10a In Diet- Induced Obesity, Insulin Resistance, And Type 2 Diabetes

Type IV P-type ATPases (P4-ATPases) are enzymes that catalyze the translocation of lipids across plasma membranes. Our lab recently discovered that Atp10a, a mammalian P4-ATPase, can translocate glucosylceramide, a sphingolipid. Both Atp10a and glucosylceramide have been independently implicated in metabolic dysfunction. To explore the role of Atp10a in metabolic dysfunction and sphingolipid metabolism, we created a novel Atp10a knockout (KO) mouse model. Atp10a KO mice display a female-specific excess weight gain on standard chow that is exacerbated by 12 weeks of high fat feeding and this is attributable to increased adiposity. Additionally, they display an accumulation of neutral lipids and altered ceramide metabolism in their livers. After a 5 hour fast, these mice exhibit elevated blood glucose levels that are not coupled to a proportional elevation in insulin levels. Atp10a KO mice also exhibit elevated plasma free fatty acids, cholesterol, and triglycerides. Thus far, our studies have shown that knocking out Atp10a in a mouse results in sex-specific perturbations to body weight and composition, glucose homeostasis, plasma lipid levels, and liver metabolism.