Year: 2024
Type: article
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.
Source: Scientific Reports
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,590
Funders: U.S. Department of Veterans Affairs, Vanderbilt University, Nihon Kohden America, National Institutes of Health, Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center, National Institute on Aging, National Heart, Lung, and Blood Institute, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G107554336, National Metabolomics Data Repository - nextgen Metabolomics Workbench, G2595216862, G3204331232, G3726302789, G3756376927, G3841187713, G3865556588, Vanderbilt Mouse Metabolic Phenotyping Center, G4148617410, G4320917349, G4513176822, LSM880-Airyscan Confocal Microscope for Large Shared Resource, G4784588152, Biomedical Data Commons Workbench (BDCW), G523589467, G5853943267, G608544753, Comprehensive Laboratory Animal Measurement System (CLAMS), G7220527126, Therapeutic Potential of Estrogen-Regulated Metabolism and Cardiovascular Risk, G879352401, G9000050522, G9000052735, G9000060478, G9000081609, G9000106052, G9000159340, Molecular and Cellular Basis for Digestive Diseases, Sex-Specific Risk of Metabolic and Cardiovascular Disease, Cancer Center Support Grant, Mechanisms of membrane homeostasis through protein and lipid transport, Vanderbilt Diabetes Research Center, Core Grant in Vision Research, Vanderbilt Student Research Training Program, Does Senescence Impair the Cardiovascular Benefits of Menopause Hormone Therapy?
OpenAlex ID: W4390570459