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Intestine‐Specific Overexpression of Carboxylesterase 2c Protects Mice From Diet‐Induced Liver Steatosis and Obesity
- Source :
- Hepatology Communications, 3(2), 227-245. JOHN WILEY & SONS LTD, Hepatology Communications
- Publication Year :
- 2018
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2018.
-
Abstract
- 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 apolipoprotcin 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.
- Subjects :
- 2. Zero hunger
0301 basic medicine
medicine.medical_specialty
Hepatology
Chemistry
Adipose tissue
Lipid metabolism
Original Articles
medicine.disease
Small intestine
3. Good health
03 medical and health sciences
Carboxylesterase
030104 developmental biology
0302 clinical medicine
Endocrinology
medicine.anatomical_structure
Internal medicine
Nonalcoholic fatty liver disease
medicine
Lipolysis
Original Article
030211 gastroenterology & hepatology
Beta oxidation
Chylomicron
Subjects
Details
- ISSN :
- 2471254X
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Hepatology Communications
- Accession number :
- edsair.doi.dedup.....ae2f2f014ca4eb932afae00994cbf609