Department of Nutrition and Health Sciences, Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan City, Taiwan; Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan; Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
J Nutr Biochem. 2021 May;91:108602. doi: 10.1016/j.jnutbio.2021.108602. Epub 2021 Feb 3.
Tomatidine is isolated from the leaves and green fruits of some plants in the Solanaceae family, and has been reported to have anti-inflammatory and antitumor effects. Previous studies have found that tomatidine decreases hepatic lipid accumulation via regulation of vitamin D receptor and activation of AMP-activated protein kinase (AMPK) phosphorylation. However, whether tomatidine reduces weight gain and improves nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated how tomatidine ameliorates NAFLD in obese mice and evaluated the regulatory mechanism of lipogenesis in hepatocytes. Male C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity and NAFLD, and treated with tomatidine via intraperitoneal injection. In vitro, FL83B hepatocytes were incubated with oleic acid and treated with tomatidine to evaluate lipid metabolism. Our results demonstrate that tomatidine significantly decreases body weight and fat weight compared to HFD-fed mice. In addition, tomatidine decreased hepatic lipid accumulation and improved hepatocyte steatosis in HFD-induced obese mice. We also found that tomatidine significantly regulated serum total cholesterol, fasting blood glucose, low-density lipoprotein, and triglyceride levels, but the serum high-density lipoprotein and adiponectin concentrations were higher than in the HFD-fed obese mice. In vivo and in vitro, tomatidine significantly suppressed the expression of fatty acid synthase and transcription factors involved in lipogenesis, and increased the expression of adipose triglyceride lipase. Tomatidine promoted the sirtuin 1 (sirt1)/AMPK signaling pathway to increase lipolysis and β-oxidation in fatty liver cells. These findings suggest that tomatidine potentially ameliorates obesity and acts against hepatic steatosis by regulating lipogenesis and the sirt1/AMPK pathway.
番茄碱是从茄科植物的叶子和绿色果实中分离出来的，具有抗炎和抗肿瘤作用。先前的研究发现，番茄碱通过调节维生素 D 受体和激活 AMP 激活的蛋白激酶（AMPK）磷酸化来减少肝脂质积累。然而，番茄碱是否能减轻体重和改善非酒精性脂肪性肝病（NAFLD）尚不清楚。在这项研究中，我们研究了番茄碱如何改善肥胖小鼠的 NAFLD，并评估了肝细胞脂肪生成的调节机制。雄性 C57BL/6 小鼠喂食高脂肪饮食（HFD）以诱导肥胖和 NAFLD，并通过腹腔注射给予番茄碱。在体外，FL83B 肝细胞用油酸孵育，并给予番茄碱处理以评估脂质代谢。我们的结果表明，与 HFD 喂养的小鼠相比，番茄碱显著降低了体重和脂肪重量。此外，番茄碱减少了 HFD 诱导肥胖小鼠的肝脂质积累和改善了肝细胞脂肪变性。我们还发现，番茄碱显著调节了血清总胆固醇、空腹血糖、低密度脂蛋白和甘油三酯水平，但血清高密度脂蛋白和脂联素浓度高于 HFD 喂养的肥胖小鼠。在体内和体外，番茄碱显著抑制了脂肪酸合成酶和参与脂肪生成的转录因子的表达，并增加了脂肪甘油三酯脂肪酶的表达。番茄碱促进了沉默调节蛋白 1（sirt1）/AMP 激活的蛋白激酶信号通路，增加了脂肪肝细胞中的脂肪分解和β-氧化。这些发现表明，番茄碱通过调节脂肪生成和 sirt1/AMPK 途径，有可能改善肥胖和对抗肝脂肪变性。
