Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Food Funct. 2020 May 1;11(5):3926-3940. doi: 10.1039/d0fo00271b. Epub 2020 May 6.
1-Deoxynojirimycin (DNJ) has been known for its functional properties, such as its anti-hyperglycemic and anti-obesity activities. Previously, we developed a sustainable procedure to produce culture broth powder (CBP) containing DNJ using Bacillus amyloliquefaciens AS385 and demonstrated its regulatory effect on the blood glucose and lipid parameters in C57BL/6J mice. The present study was aimed to determine the molecular mechanism underlying the physiological effects of CBP intake in different concentrations (low, medium and high) towards the development of high-fat diet (HFD)-induced metabolic disorders. Ten-week consumption of CBP-supplemented diets ameliorated HFD-induced adiposity, glucose intolerance, and reduced insulin sensitivity in C57BL/6J mice. To investigate how these physiological events could take place, we analyzed the expression of genes involved in lipid metabolism and insulin signaling in epididymal white adipose tissue and found that CBP had a regulatory effect on the expression of genes related to lipid metabolism (Pparγ, Srebf1c, Acc, Scd, Hsl, Lpl), adiponectin secretion (Foxo1 and Sirt1), and insulin signaling (Irs1 and Akt2). Next, we confirmed that DNJ acted as the main active component in CBP and detected the dose-dependent DNJ uptake in vital metabolic tissues, which may explain the dose-dependent alteration in the metabolic parameters and related gene expressions following the CBP intake in this study. Collectively, our results suggested that DNJ intake in the form of CBP prevented the progression of HFD-induced metabolic disorders through regulation of adipocyte gene expression involved in lipid metabolism and insulin signaling.
1-脱氧野尻霉素(DNJ)以其功能特性而闻名,例如其抗高血糖和抗肥胖活性。此前,我们使用解淀粉芽孢杆菌 AS385 开发了一种可持续的生产含有 DNJ 的培养肉汤粉(CBP)的方法,并证明了其对 C57BL/6J 小鼠血糖和血脂参数的调节作用。本研究旨在确定 CBP 以不同浓度(低、中、高)摄入对高脂肪饮食(HFD)诱导的代谢紊乱发展的生理作用的分子机制。10 周的 CBP 补充饮食可改善 C57BL/6J 小鼠的肥胖、葡萄糖不耐受和胰岛素敏感性降低。为了研究这些生理事件是如何发生的,我们分析了附睾白色脂肪组织中与脂质代谢和胰岛素信号相关的基因表达,发现 CBP 对与脂质代谢(Pparγ、Srebf1c、Acc、Scd、Hsl、Lpl)、脂联素分泌(Foxo1 和 Sirt1)和胰岛素信号(Irs1 和 Akt2)相关的基因表达具有调节作用。接下来,我们证实 DNJ 是 CBP 中的主要活性成分,并检测到关键代谢组织中 DNJ 的剂量依赖性摄取,这可能解释了本研究中 CBP 摄入后代谢参数和相关基因表达的剂量依赖性变化。总之,我们的结果表明,CBP 形式的 DNJ 通过调节参与脂质代谢和胰岛素信号的脂肪细胞基因表达来预防 HFD 诱导的代谢紊乱的进展。