datasheet1_Gallic Acid Ameliorated Impaired Lipid Homeostasis in a Mouse Model of High-Fat Diet—and Streptozotocin-Induced NAFLD and Diabetes through Improvement of β-oxidation and Ketogenesis.docx

Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice. HFD and STZ induced severe diabetes, NAFLD, and other metabolic disorders in mice. However, the results of liver histopathology and serum biochemical examinations indicated that daily GA treatment alleviated the high blood glucose levels in the mice and decelerated the progression of NAFLD. In addition, our results show that the hepatoprotective effect of GA in diabetic mice occurs in part through a partially preventing disordered metabolic pathway related to glucose, lipids, amino acids, purines, and pyrimidines. Specifically, the mechanism responsible for alleviation of lipid accumulation is related to the upregulation of β-oxidation and ketogenesis. These findings indicate that GA alleviates metabolic diseases through novel mechanisms.

没食子酸（GA）是一类存在于食物与传统中药中的简单多酚类化合物。本研究旨在探究GA给药对高脂饮食（HFD）诱导肥胖联合低剂量链脲佐菌素（STZ）诱导高血糖小鼠模型的干预效应，该模型可模拟非酒精性脂肪性肝病（NAFLD）与2型糖尿病共存的病理状态。研究结合生理评估、病理学检查、血液、尿液、肝脏及肌肉组织的代谢组学分析以及基因表达检测结果，试图阐明GA在高血糖与血脂异常小鼠中的治疗效果及其潜在作用机制。HFD联合STZ造模可使小鼠出现严重糖尿病、NAFLD及其他代谢紊乱症状。但肝脏组织病理学与血清生化检测结果显示，每日GA给药可缓解小鼠的高血糖水平，并延缓NAFLD的病情进展。此外，本研究结果表明，GA对糖尿病小鼠的保肝作用部分通过阻断葡萄糖、脂质、氨基酸、嘌呤及嘧啶相关的代谢通路紊乱实现。具体而言，其缓解脂质堆积的作用机制与上调β氧化与生酮作用相关。上述研究结果提示，GA可通过全新的作用机制改善代谢性疾病。