State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China.
Int J Biol Sci. 2022 Sep 11;18(15):5740-5752. doi: 10.7150/ijbs.74348. eCollection 2022.
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 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.
小肠是外源性脂质消化和吸收的主要部位，对脂质代谢稳态很重要。细胞死亡诱导 DNA 片段化因子样效应物 C（CIDEC）在肠道以外的组织中活跃于脂质代谢。我们通过 Cre/LoxP 重组开发了小肠特异性 CIDEC（SI-CIDEC）敲除 C57BL/6J 小鼠，以研究肠道 CIDEC 对脂质代谢的影响。喂食高脂肪饮食 14 周的 8 周龄 SI-CIDEC 小鼠的体重降低了 15%，体脂肪质量降低了 30%，肝甘油三酯（TG）降低了 79%，而野生型（WT）小鼠则没有。此外，与喂食高脂肪饮食的野生型小鼠相比，敲除小鼠的肝脂肪变性和脂肪肝炎症程度较轻。与野生型小鼠相比，喂食高脂肪饮食的 SI-CIDEC 小鼠的血清 TG 更低，粪便 TG 和肠道脂肪酶活性更高。机制研究表明，CIDEC 通过与 1-酰基甘油-3-磷酸-O-酰基转移酶相互作用加速了磷脂酸的合成，从而促进了 TG 的积累。这项研究确定了一个新的相互作用蛋白和以前未报道的 CIDEC 机制，揭示了其在小肠脂质代谢中的活性。
