1-脱氧野尻霉素对肥胖小鼠脂代谢的影响及机理

探究1-脱氧野尻霉素(1-deoxynojirimycin,DNJ)对营养性肥胖的脂代谢调控作用及其途径,旨在为开发DNJ降糖、降脂减肥产品提供依据。通过饲喂高脂饲料建立肥胖小鼠模型,之后喂食普通饲料40 d,同时实验组灌胃不同剂量(8.0、4.0、2.0 mg/(kg·d),以体质量计)DNJ,用酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法测定小鼠的血脂水平、脂肪细胞因子、脂肪酸合成及氧化过程中相关酶活力。结果显示,与阴性对照组比较,在8.0 mg/(kg·d)剂量组中DNJ可使雌、雄鼠体质量分别下降9.06%、14.07%,肝脂含量分别下降4.13%、27.82%,腹腔脂肪系数分别下降9.00%、34.30%,血清总胆固醇含量分别下降11.57%、35.13%,总甘油三酯含量分别下降46.89%、30.65%,高密度脂蛋白含量分别增加28.86%、7.00%,游离脂肪酸含量分别下降10.60%、10.20%,内脂素含量分别下降38.44%、26.76%,脂联素含量分别上升29.66%、26.96%,肝脏中乙酰辅酶A羧化酶活力分别下降17.03%、15.52%,脂肪酸合成酶活力分别下降23.53%、21.13%,肉毒碱脂酰转移酶Ⅰ活力分别上升20.38%、17.20%,酰基辅酶A氧化酶活力分别上升11.00%、16.29%。上述结果表明,肥胖小鼠在控制饮食的同时摄入适量DNJ可以有效控制脂肪的合成、促进脂肪的氧化分解,达到调控血脂、减少脂肪积累、控制体质量的目的。DNJ对雌、雄鼠脂代谢调控的作用途径不同,其对雄鼠的降脂效果更显著。

Effect and Mechanism of 1-Deoxynojirimycin on Lipid Metabolism in Obese Mice

This study explored the regulatory effect of 1-deoxynojirimycin (DNJ) on lipid metabolism in obese mechanism rats as well as the underlying mechanism of action to provide valuable information for the development of DNJ-based antilipemic and antidiabetic agents. An obese mouse model was created by feeding mice on a high-fat diet, and then all mice were fed on a normal diet for 40 days. During this period, the animals in the experimental groups were gavaged with DNJ at different doses (8.0, 4.0 and 2.0 mg/ (kg·d)). At the end, serum biochemical indicators, serum adipocytokines, and the enzyme activities involved in the synthesis and oxidation of fatty acids were determined by enzyme linked immunosorbent assay (ELISA) kits. Compared with the negative control group, DNJ at 8.0 mg/(kg·d) reduced the body weight of obese female and male mice by 9.06% and 14.07%, decreased liver fat content by 4.13% and 27.82%, intra-abdominal fat to body weight ratio by 9.00% and 34.30%, serum total cholesterol (TC) level by 11.57% and 35.13%, triglyceride level by 46.89% and 30.65%, high-density lipoprotein (HDL) level by 28.86% and 7.00%, free fatty acid (FFA) content by 10.60% and 10.20% and visfatin level by 38.44% and 26.76%, increased adiponectin level by 29.66% and 26.96%, decreased acetyl CoA carboxylasec (ACC) activity in the liver by 17.03% and 15.52% and fatty acid synthetasein (FAS) activity by 23.53% and 21.13%, and elevated carnitine palmitoyl transferase (CPT) activity by 20.38% and 17.20% and acyl-CoA oxidase (ACO) activity by 11.00% and 16.29%, respectively. These results suggested that when combined with less energy intake, DNJ can improve blood lipid levels, reduce fat accumulation and control body weight by inhibiting fatty acid synthesis and accelerating fatty acid oxidation. In addition, DNJ has a better effect on male mice than female ones.