Soat2 ties cholesterol metabolism to ß-oxidation and glucose tolerance in male mice.
J Intern Med
; 292(2): 296-307, 2022 08.
Article
in En
| MEDLINE
| ID: mdl-34982494
ABSTRACT
BACKGROUND:
Sterol O-acyltransferase 2 (Soat2) encodes acyl-coenzyme Acholesterol 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sterol O-Acyltransferase
/
Fatty Liver
/
Insulins
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Intern Med
Journal subject:
MEDICINA INTERNA
Year:
2022
Document type:
Article
Affiliation country:
Sweden