Wu Hung-Tsung, Lin Ching-Han, Pai Hsiu-Ling, Chen Yi-Cheng, Cheng Kai-Pi, Kuo Hsin-Yu, Li Chung-Hao, Ou Horng-Yih
Department of Internal Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan City, Taiwan.
Front Nutr. 2022 May 23;9:823723. doi: 10.3389/fnut.2022.823723. eCollection 2022.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, and it is strongly associated with obesity. To combat obesity, artificial sweeteners are often used to replace natural sugars, and sucralose is one of the most extensively used sweeteners. It was known that sucralose exerted effects on lipid metabolism dysregulation, and hepatic inflammation; however, the effects of sucralose on hepatic steatosis were still obscure. In this study, we found that supplements of sucralose enhanced high-fat-diet (HFD)-induced hepatic steatosis. In addition, treatment of sucralose increased reactive oxygen species (ROS) generation and induced endoplasmic reticulum (ER) stress in HepG2 cells. Pretreatment of ROS or ER stress inhibitors reversed the effects of sucralose on lipogenesis. Furthermore, pretreatment of taste receptor type 1 membrane 3 (T1R3) inhibitor or T1R3 knockdown reversed sucralose-induced lipogenesis in HepG2 cells. Taken together, sucralose might activate T1R3 to generate ROS and promote ER stress and lipogenesis, and further accelerate to the development of hepatic steatosis.
非酒精性脂肪性肝病（NAFLD）是全球最常见的慢性肝病，且与肥胖密切相关。为对抗肥胖，人们常使用人工甜味剂替代天然糖，三氯蔗糖是使用最广泛的甜味剂之一。已知三氯蔗糖会对脂质代谢失调及肝脏炎症产生影响；然而，三氯蔗糖对肝脏脂肪变性的影响仍不明确。在本研究中，我们发现补充三氯蔗糖会加剧高脂饮食（HFD）诱导的肝脏脂肪变性。此外，三氯蔗糖处理会增加HepG2细胞中活性氧（ROS）的生成并诱导内质网（ER）应激。ROS或ER应激抑制剂预处理可逆转三氯蔗糖对脂肪生成的影响。此外，味觉受体1型膜3（T1R3）抑制剂预处理或T1R3基因敲低可逆转三氯蔗糖诱导的HepG2细胞脂肪生成。综上所述，三氯蔗糖可能激活T1R3以产生活性氧并促进内质网应激和脂肪生成，进而加速肝脏脂肪变性的发展。
