Journal article
Soat2 ties cholesterol metabolism to β-oxidation and glucose tolerance in male mice
- Abstract:
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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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 937.6KB, Terms of use)
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- Publisher copy:
- 10.1111/joim.13450
Authors
- Publisher:
- Wiley
- Journal:
- Journal of Internal Medicine More from this journal
- Volume:
- 292
- Issue:
- 2
- Pages:
- 296-307
- Publication date:
- 2022-01-13
- Acceptance date:
- 2022-01-04
- DOI:
- EISSN:
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1365-2796
- ISSN:
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0954-6820
- Pmid:
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34982494
- Language:
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English
- Keywords:
- Pubs id:
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1231454
- Local pid:
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pubs:1231454
- Deposit date:
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2022-01-18
- ARK identifier:
Terms of use
- Copyright holder:
- Pramfalk et al.
- Copyright date:
- 2022
- Rights statement:
- © 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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