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Article Dans Une Revue Journal of Internal Medicine Année : 2022

Soat2 ties cholesterol metabolism to β‐oxidation and glucose tolerance in male mice

Résumé

Background: Sterol O-acyltransferase 2 (Soat2) encodes acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2), which synthesizes cholesteryl esters in hepatocytes and enterocytes fated either to storage or to secretion into nascent triglyceride-rich lipoproteins. Objectives: We aimed to unravel the molecular mechanisms leading to reduced hepatic steatosis when Soat2 is depleted in mice. Methods: Soat2−/− and wild-type mice were fed a high-fat, a high-carbohydrate, or a chow diet, and parameters of lipid and glucose metabolism were assessed. Results: Glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), oral glucose tolerance (OGTT), and insulin tolerance tests significantly improved in Soat2−/− mice, irrespective of the dietary regimes (2-way ANOVA). The significant positive correlations between area under the curve (AUC) OGTT (r = 0.66, p < 0.05), serum fasting insulin (r = 0.86, p < 0.05), HOMA-IR (r = 0.86, p < 0.05), Adipo-IR (0.87, p < 0.05), hepatic triglycerides (TGs) (r = 0.89, p < 0.05), very-low-density lipoprotein (VLDL)-TG (r = 0.87, p < 0.05) and the hepatic cholesteryl esters in wild-type mice disappeared in Soat2−/− mice. Genetic depletion of Soat2 also increased whole-body oxidation by 30% (p < 0.05) compared to wild-type mice. Conclusion: Our data demonstrate that ACAT2-generated cholesteryl esters negatively affect the metabolic control by retaining TG in the liver and that genetic inhibition of Soat2 improves liver steatosis via partitioning of lipids into secretory (VLDL-TG) and oxidative (fatty acids) pathways.
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Dates et versions

hal-03835807 , version 1 (01-11-2022)

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Camilla Pramfalk, Osman Ahmed, Matteo Pedrelli, Mirko Minniti, Serge Luquet, et al.. Soat2 ties cholesterol metabolism to β‐oxidation and glucose tolerance in male mice. Journal of Internal Medicine, 2022, 292 (2), pp.296-307. ⟨10.1111/joim.13450⟩. ⟨hal-03835807⟩
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