SCD1 is a key enzyme controlling lipid metabolism and a link between its activity and NAFLD has been proposed. Lipophagy is a novel regulatory approach to lipid metabolism regulation, which is involved in the development of NAFLD. However, the possible functional connection between SCD1 and lipophagy in NAFLD remains unknown. To investigate the molecular mechanisms through which SCD1 regulates lipophagy in hepatic steatosis, the model of hepatic steatosis was established by inducing mouse primary hepatocytes with sodium palmitate and feeding C57BL/6 mice with HFD. Our results indicated that sodium palmitate-treated hepatocytes exhibited increased SCD1 expression, AMPK inactivation and defective lipophagy. Inhibition of SCD1 expression in hepatocytes resulted in enhanced AMPK activity and lipophagy, and reduced lipid deposition. Although SCD1 overexpression led to decreased AMPK activity and lipophagy, lipid deposition was increased in hepatocytes. SCD1 regulated lipophagy through AMPK to affect lipid metabolism in mouse primary hepatocytes. Additionally, compared to HFD-fed mice, CAY10566(an SCD1-specific inhibitor)-treated mice exhibited significantly decreased hepatic steatosis and hepatic lipid droplet accumulation, as well as enhanced AMPK activity and lipophagy. This study elucidated that SCD1 inhibition ameliorates hepatic steatosis by inducing AMPK-mediated lipophagy, suggesting that the SCD1-AMPK-lipophagy pathway is a potential therapeutic target for NAFLD.

The aim of this study was to investigate how the signaling pathway downstream of mTOR/S6K1 contributes to the regulation of SREBP-1c expression during lipogenesis in HepG2 cells. The model of steatosis was established using human hepatocytes HepG2 and inducting them with sodium palmitate. mTOR, S6K1 and LXRα were inhibited by rapamycin, PF-4708671 and siRNA-LXRα, respectively. After a variety of different treatment, the levels of intracellular triglycerides, the accumulation of lipid droplets and the expression levels of related genes were detected. Rapamycin, PF-4708671 and siRNA-LXRα treatment could decrease the accumulation of triglycerides and lipid droplets induced by sodium palmitate in HepG2 cells, and the inhibitory effect could be enhanced by the combination of them. Sodium palmitate stimulated the expression of genes encoding mTOR, S6K1, LXRα, SREBP-1c and SREBP-1c target enzymes (FAS and ACC1) in HepG2 cells. Moreover, these genes were sensitive to rapamycin. PF-4708671 also decreased the expression of these genes, except for the mTOR gene, and the extent of reduction could be enhanced by combination with rapamycin. Knockdown of LXRα decreased the expression of SREBP-1c, FAS and ACC1, but it had no effect on the expression of mTOR or S6K1. Furthermore, rapamycin and PF-4708671 enhanced the inhibitory effect of siRNA-LXRα. mTOR/S6K1 regulates the SREBP-1c signaling pathway through LXRα in sodium palmitate-induced HepG2 cells, suggesting LXRα might be a potential therapeutic target for NAFLD.

Effective wound closure is key for a successful endoscopic full-thickness resection (EFTR). The currently available titanium clips can only be used to close wounds of <2 cm [1], the over-the-scope (OTS) clip device requires a series of complex operations [2], and, although the novel through-the-scope twin endoclip (TTS-TC) device is simple and rapid in operation, it is expensive [3]. Based on the principle of the TTS-TC, a three-arm clip (TAC), which is economical, easy to use, and suitable for the closure of large mucosal or submucosal wounds (>3 cm), was made by our team by binding two titanium clips together. A 68-year-old man was found on gastroscopy to have a submucosal protrusive lesion in the posterior wall of the upper gastric body. Endoscopic ultrasound confirmed that the lesion was originating from the muscularis propria. EFTR was performed to resect the submucosal tumor, leaving a wound of about 3.5 × 3.0 cm. Herein, we present the successful closure of this large wound with our self-made TAC, using the following steps. First, a transparent cap with a groove was created and place on the tip of the endoscope ([Fig. 1] a). Second, two titanium clips were placed inside and outside of the transparent cap ([Fig. 1] b). The two clips were opened, with one jaw of each clip tied together with surgical suture ([Fig. 1] c). The bound clips were accurately placed on either side of the groove in the cap ([Fig. 1] d). After the wound had been fully exposed ([Fig. 2] a), the TAC was delivered to the site of the wound with the help of an assistant ([Fig. 2] b). With the use of this technique, the large wound on the posterior wall of the upper gastric body was successfully turned into two smaller wounds ([Fig. 2] c–e). The decreased wound sizes following use of the TAC meant traditional clips could subsequently be conveniently used to completely close the wound ([Video 1]). Endoscopy_UCTN_Code_TTT_1AO_2AI Article published online: 01 March 2024 © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/). Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany