Int J Biol Sci 2022; 18(15):5740-5752. doi:10.7150/ijbs.74348 This issue

Research Paper

Small Intestine-specific Knockout of CIDEC Improves Obesity and Hepatic Steatosis by Inhibiting Synthesis of Phosphatidic Acid

Liang Huang, Qichao Liao, Tingli Pan, Yu Sun, Zhier Aluo, Lianggui Xiao, Jingsu Yu, Siqi Liu, Yang Xiao, Yufeng Yang, Yixing Li, Lei Zhou

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, China.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Huang L, Liao Q, Pan T, Sun Y, Aluo Z, Xiao L, Yu J, Liu S, Xiao Y, Yang Y, Li Y, Zhou L. Small Intestine-specific Knockout of CIDEC Improves Obesity and Hepatic Steatosis by Inhibiting Synthesis of Phosphatidic Acid. Int J Biol Sci 2022; 18(15):5740-5752. doi:10.7150/ijbs.74348. Available from https://www.ijbs.com/v18p5740.htm

File import instruction

Abstract

Graphic abstract

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.

Keywords: obesity, hepatic steatosis, small intestine, CIDEC, lipid absorption phosphatidic acid