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Deficiency of the lipid flippase ATP10A causes diet-induced dyslipidemia in female mice.
Norris, Adriana C; Yazlovitskaya, Eugenia M; Zhu, Lin; Rose, Bailey S; May, Jody C; Gibson-Corley, Katherine N; McLean, John A; Stafford, John M; Graham, Todd R.
Afiliación
  • Norris AC; Department of Biological Sciences, Vanderbilt University, 465 21St Ave S, Nashville, TN, 37212, USA.
  • Yazlovitskaya EM; Department of Biological Sciences, Vanderbilt University, 465 21St Ave S, Nashville, TN, 37212, USA.
  • Zhu L; Division of Endocrinology, Diabetes and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Rose BS; Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
  • May JC; Center for Innovative Technology, Vanderbilt University, Nashville, TN, USA.
  • Gibson-Corley KN; Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
  • McLean JA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, USA.
  • Stafford JM; Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN, USA.
  • Graham TR; Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
Sci Rep ; 14(1): 343, 2024 01 03.
Article en En | MEDLINE | ID: mdl-38172157
ABSTRACT
Genetic association studies have linked ATP10A and closely related type IV P-type ATPases (P4-ATPases) to insulin resistance and vascular complications, such as atherosclerosis. ATP10A translocates phosphatidylcholine and glucosylceramide across cell membranes, and these lipids or their metabolites play important roles in signal transduction pathways regulating metabolism. However, the influence of ATP10A on lipid metabolism in mice has not been explored. Here, we generated gene-specific Atp10A knockout mice and show that Atp10A-/- mice fed a high-fat diet did not gain excess weight relative to wild-type littermates. However, Atp10A-/- mice displayed female-specific dyslipidemia characterized by elevated plasma triglycerides, free fatty acids and cholesterol, as well as altered VLDL and HDL properties. We also observed increased circulating levels of several sphingolipid species along with reduced levels of eicosanoids and bile acids. The Atp10A-/- mice also displayed hepatic insulin resistance without perturbations to whole-body glucose homeostasis. Thus, ATP10A has a sex-specific role in regulating plasma lipid composition and maintaining hepatic liver insulin sensitivity in mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Dislipidemias Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Dislipidemias Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido