期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 18, 期 15, 页码 5740-5752出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.74348
关键词
obesity; hepatic steatosis; small intestine; CIDEC; lipid absorption phosphatidic acid
资金
- Guangxi Natural Science Foundation [2019GXNSF DA245029]
- Guangxi Science Foundation for Distinguished Young Scholars [2020GXNSFFA297008]
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources [SKLCUSA-a202006]
- Training Project of High-Level Professional and Technical Talents of
- Training Project of High-Level Professional and Technical Talents of Guangxi University
This study highlights the importance of CIDEC in lipid metabolism, particularly in the small intestine. Knockout mice with a specific deletion of CIDEC in the small intestine showed improved lipid metabolism, including decreased body weight, body fat mass, and liver triglycerides. Mechanistic studies revealed that CIDEC interacts with 1-acylglycerol-3-phosphate-O-acyltransferase to promote phosphatidic acid synthesis and TG accumulation.
The small intestine is main site of exogenous lipid digestion and absorption, and it is important for lipid metabolic homeostasis. Cell death-inducing DNA fragmentation-factor like effector C (CIDEC) is active in lipid metabolism in tissues other than those in the intestine. We developed small intestine-specific CIDEC (SI-CIDEC-/- ) knockout C57BL/6J mice by Cre/LoxP recombination to investigate the in vivo effects of intestinal CIDEC on lipid metabolism. Eight-week-old SI-CIDEC(-/- )mice fed a high-fat diet for 14 weeks had 15% lower body weight, 30% less body fat mass, and 79% lower liver triglycerides (TG) than wild-type (WT) mice. In addition, hepatic steatosis and fatty liver inflammation were less severe in knockout mice fed a high-fat diet (HFD) compared with wild-type mice fed an HFD. SI-CIDEC-/- mice fed an HFD diet had lower serum TG and higher fecal TG and intestinal lipase activity than wild-type mice. Mechanistic studies showed that CIDEC accelerated phosphatidic acid synthesis by interacting with 1-acylglycerol-3-phosphate-O-acyltransferase to promote TG accumulation. This study identified a new interacting protein and previously unreported CIDEC mechanisms that revealed its activity in lipid metabolism of the small intestine.
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