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

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.

Arbutin alleviates fatty liver by inhibiting ferroptosis via FTO/SLC7A11 pathway

“…At least 3 mice are randomly selected from each group for metabolic cage (Promethion Cages, Sable Systems International, Las Vegas, Nevada, U.S.A.) experiments. Metabolic cages recorded exercise, O 2 consumption, CO 2 production, respiratory exchange rate (RER), and energy expenditure at 5 min intervals for 48 h as previously described [ 19 ].…”

Genome Sequencing Provides Novel Insights into Mudflat Burrowing Adaptations in Eel Goby Taenioides sp. (Teleost: Amblyopinae)

“…( Table S17 ). The enrichment categories of the top PSGs were associated with hematopoiesis or angiogenesis ( TSPAN33 , GATA4 , and FBLN5 ) [ 18 , 19 , 20 ], DNA repairs ( POLD2 , XPCC , and EXO1 ) [ 21 , 22 , 23 ], immune response ( C1QTNF1 , IFI30 and IFIH1 ) [ 24 , 25 , 26 ], and carbohydrate/lipid metabolism ( PGLS , ECHS1 , CIDEC, CELA2A, and CCDC186 ) [ 27 , 28 , 29 , 30 , 31 ] ( Figure 3 , Tables S18 and S19 ). The evidence of positive selection in genes associated with hematopoiesis or angiogenesis, DNA repairs, immune response, and carbohydrate/lipid metabolism may indicate a role of remolding of circulatory, immune, and metabolic systems of Taenioides sp.…”

Deletion of the mitochondrial calcium uniporter in adipose tissue promotes energy expenditure and alleviates diet-induced obesity

“…Mice were anaesthetized by intraperitoneal injection of tribromoethanol (TCI; Shanghai China), placed supine in a scanning chamber, and analyzed for fat distribution by micro-computed tomography (Bruke SkyScan 1278; Bielerica, Massachusetts, USA) [ 27 ]. Scan results were acquired with reconstruction software (NRECON) and analysis software (Dataviewer, CTVOX, CTAN) [ 28 ].…”