Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
Department of Hepatology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China.
Can J Physiol Pharmacol. 2021 Aug;99(8):775-785. doi: 10.1139/cjpp-2020-0259. Epub 2020 Dec 8.
Theobromine, a methylxanthine present in cocoa, has been shown to possess many beneficial pharmacological properties such as anti-oxidative stress, anti-inflammatory property, and anti-microbial activity. In this study, we investigated the effects of theobromine on nonalcoholic fatty liver disease (NAFLD) and the possible underlying mechanisms in vivo and in vitro. The results showed that theobromine reduced body weight and fat mass and improved dyslipidemia. Theobromine mitigated liver injury and significantly reduced hepatic triglyceride level in mice with obesity. Histological examinations also showed hepatic steatosis was alleviated after theobromine treatment. Furthermore, theobromine reversed the elevated mRNA and protein expression of SREBP-1c, FASN, CD36, FABP4, and the suppressed expression of PPARα and CPT1a in the liver of mice with obesity, which were responsible for lipogenesis, fatty acid uptake, and fatty acid oxidation respectively. In vitro, theobromine also downregulated SREBP-1c, FASN, CD36, FABP4 and upregulated PPARα and CPT1a mRNA and protein levels in hepatocytes in a dose-dependent manner, while these changes were reversed by L-leucine, a mammalian target of rapamycin (mTOR) agonist. The present study demonstrated that theobromine improved NAFLD by inhibiting lipogenesis and fatty acid uptake and promoting fatty acid oxidation in the liver and hepatocytes, which might be associated with its suppression of mTOR signaling pathway. Theobromine protects against high-fat diet - induced NAFLD. Theobromine inhibits lipogenesis and fatty acid uptake and promotes fatty acid oxidation in the liver and hepatocytes via inhibiting mTOR signaling pathway.
可可中的甲基黄嘌呤——可可碱，已被证明具有多种有益的药理特性，如抗氧化应激、抗炎和抗微生物活性。在这项研究中，我们在体内和体外研究了可可碱对非酒精性脂肪性肝病（NAFLD）的影响及其可能的潜在机制。结果表明，可可碱可降低体重和脂肪量，改善血脂异常。可可碱可减轻肥胖小鼠的肝损伤，显著降低肝甘油三酯水平。组织学检查还表明，可可碱治疗后肝脂肪变性得到缓解。此外，可可碱逆转了肥胖小鼠肝脏中 SREBP-1c、FASN、CD36、FABP4 的 mRNA 和蛋白表达升高，以及 PPARα 和 CPT1a 的表达降低，这些蛋白分别负责脂肪生成、脂肪酸摄取和脂肪酸氧化。在体外，可可碱也以剂量依赖的方式下调了肝细胞中 SREBP-1c、FASN、CD36、FABP4 的 mRNA 和蛋白水平，上调了 PPARα 和 CPT1a 的 mRNA 和蛋白水平，而这些变化被 mTOR 激动剂 L-亮氨酸逆转。本研究表明，可可碱通过抑制肝脏和肝细胞中的脂肪生成和脂肪酸摄取，促进脂肪酸氧化，改善了 NAFLD，这可能与其抑制 mTOR 信号通路有关。可可碱可预防高脂肪饮食诱导的非酒精性脂肪性肝病。可可碱通过抑制 mTOR 信号通路，抑制脂肪生成和脂肪酸摄取，促进肝脏和肝细胞中的脂肪酸氧化。
