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

Citations Over TimeTop 10% of 2022 papers

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.

Related Papers

• → Effect of ractopamine on lipid metabolism in vivo - a systematic review(2013)28 cited
• → The simple method of lipolysis/lipogenesis balance assessment based on 14C isotope: advances and importance of pH control(2023)4 cited
• → Effects of Ginseng Saponins on the Actions of Adrenaline, ACTH and Insulin on Lipolysis and Lipogenesis in Adipose Tissue(1981)15 cited
• → Differential control of lipogenesis and lipolysis during development of ovine preadipocytesin vitro(2006)2 cited
• → Regulation of Fatty Acid Biosynthesis and Lipolysis(2001)4 cited