| Autor: |
Maresch LK; Institute of Molecular Biosciences University of Graz Graz Austria., Benedikt P; Institute of Molecular Biosciences University of Graz Graz Austria., Feiler U; Institute of Molecular Biosciences University of Graz Graz Austria., Eder S; Institute of Molecular Biosciences University of Graz Graz Austria., Zierler KA; Institute of Molecular Biosciences University of Graz Graz Austria., Taschler U; Institute of Molecular Biosciences University of Graz Graz Austria., Kolleritsch S; Institute of Molecular Biosciences University of Graz Graz Austria., Eichmann TO; Institute of Molecular Biosciences University of Graz Graz Austria., Schoiswohl G; Institute of Molecular Biosciences University of Graz Graz Austria., Leopold C; Gottfried Schatz Research Center, Molecular Biology and Biochemistry Medical University of Graz Graz Austria., Wieser BI; Diagnostic & Research Center for Molecular BioMedicine Institute of Pathology Medical University of Graz Graz Austria., Lackner C; Diagnostic & Research Center for Molecular BioMedicine Institute of Pathology Medical University of Graz Graz Austria., Rülicke T; Institute of Laboratory Animal Science University of Veterinary Medicine Wien Austria., van Klinken J; Department of Human Genetics Leiden University Medical Centre Leiden the Netherlands., Kratky D; Gottfried Schatz Research Center, Molecular Biology and Biochemistry Medical University of Graz Graz Austria., Moustafa T; Division of Gastroenterology and Hepatology Medical University Graz Graz Austria., Hoefler G; Diagnostic & Research Center for Molecular BioMedicine Institute of Pathology Medical University of Graz Graz Austria., Haemmerle G; Institute of Molecular Biosciences University of Graz Graz Austria. |
| Jazyk: |
angličtina |
| Zdroj: |
Hepatology communications [Hepatol Commun] 2018 Dec 17; Vol. 3 (2), pp. 227-245. Date of Electronic Publication: 2018 Dec 17 (Print Publication: 2019). |
| DOI: |
10.1002/hep4.1292 |
| Abstrakt: |
Murine hepatic carboxylesterase 2c ( Ces2c ) and the presumed human ortholog carboxylesterase 2 ( CES2 ) have been implicated in the development of nonalcoholic fatty liver disease (NAFLD) in mice and obese humans. These studies demonstrated that Ces2c hydrolyzes triglycerides (TGs) in hepatocytes. Interestingly, Ces2c / CES2 is most abundantly expressed in the intestine, indicating a role of Ces2c / CES2 in intestinal TG metabolism. Here we show that Ces2c is an important enzyme in intestinal lipid metabolism in mice. Intestine-specific Ces2c overexpression (Ces2c int ) provoked increased fatty acid oxidation (FAO) in the small intestine accompanied by enhanced chylomicron clearance from the circulation. As a consequence, high-fat diet-fed Ces2c int mice were resistant to excessive diet-induced weight gain and adipose tissue expansion. Notably, intestinal Ces2c overexpression increased hepatic insulin sensitivity and protected mice from NAFLD development. Although lipid absorption was not affected in Ces2c int mice, fecal energy content was significantly increased. Mechanistically, we demonstrate that Ces2c is a potent neutral lipase, which efficiently hydrolyzes TGs and diglycerides (DGs) in the small intestine, thereby generating fatty acids (FAs) for FAO and monoglycerides (MGs) and DGs for potential re-esterification. Consequently, the increased availability of MGs and DGs for re-esterification and primordial apolipoprotein B 48 particle lipidation may increase chylomicron size, ultimately mediating more efficient chylomicron clearance from the circulation. Conclusion: This study suggests a critical role for Ces2c in intestinal lipid metabolism and highlights the importance of intestinal lipolysis to protect mice from the development of hepatic insulin resistance, NAFLD, and excessive diet-induced weight gain during metabolic stress. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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