Department of Comparative Medicine, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.College of Pharmacy; University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Department of Pharmaceutical Sciences, College of Pharmacy; University of Tennessee Health Science Center, Memphis, Tennessee, USA.
J Med Food. 2022 Jun;25(6):607-617. doi: 10.1089/jmf.2021.0196.
The objective of this study was to identify alterations in lipids and polyunsaturated fatty acid (PUFA) metabolism in both the streptozotocin (STZ)-induced type 1 diabetic (T1D) mouse and the mutant type 2 diabetic (T2D) mouse to establish a biological signature for the evaluation of natural products with purported lipid-altering activity. Eight-week-old male C57BL/6J mice were randomized to nondiabetic group or STZ-induced diabetic groups ( = 10/group). STZ-induced diabetic mice and 6-week-old male mice ( = 10/group) were randomized to the following groups: (1) diabetic control, no treatment, (2) methylsulfonylmethane (MSM) treatment, (3) sesame seed oil (SSO) treatment, and (4) MSM+SSO combination treatment. Clinical parameters measured included weights, blood glucose, serum lipid panels, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection of free fatty acids in serum, liver, brain, and eyes. Blood glucose significantly decreased after 4 weeks of MSM treatment in T1D mice. Serum PUFA levels were significantly reduced in T2D mice compared with control mice. In contrast, treatment with SSO reversed this effect in T2D mice, exhibiting serum PUFA levels comparable to control mice. Serum triglycerides were significantly increased in both diabetic models compared to nondiabetic control, mimicking diabetes in people. High-density lipoprotein (HDL) was significantly increased in T1D receiving MSM+SSO and all T2D treatment groups. A corresponding significant decrease in non-HDL cholesterol was seen in T2D mice in all treatment groups. MSM+SSO treatment's effects on HDL and non-HDL cholesterol and PUFA metabolism could lead to improved clinical outcomes in diabetics by improving the lipid profile.
本研究旨在鉴定链脲佐菌素（STZ）诱导的 1 型糖尿病（T1D）小鼠和突变型 2 型糖尿病（T2D）小鼠中脂质和多不饱和脂肪酸（PUFA）代谢的改变，为评估具有潜在脂质改变活性的天然产物建立生物学特征。将 8 周龄雄性 C57BL/6J 小鼠随机分为非糖尿病组或 STZ 诱导的糖尿病组（每组 10 只）。将 STZ 诱导的糖尿病小鼠和 6 周龄雄性 小鼠（每组 10 只）随机分为以下组：（1）糖尿病对照组，无治疗；（2）甲磺酰甲烷（MSM）治疗组；（3）芝麻油（SSO）治疗组；（4）MSM+SSO 联合治疗组。测量的临床参数包括体重、血糖、血清脂质谱以及血清、肝脏、大脑和眼睛中游离脂肪酸的液相色谱-串联质谱（LC-MS/MS）检测。在 T1D 小鼠中，MSM 治疗 4 周后血糖显著下降。与对照组相比，T2D 小鼠的血清 PUFA 水平显著降低。相比之下，SSO 治疗可逆转 T2D 小鼠的这种作用，使其血清 PUFA 水平与对照组相当。与非糖尿病对照组相比，两种糖尿病模型的血清甘油三酯均显著升高，模拟了人类的糖尿病。高密度脂蛋白（HDL）在接受 MSM+SSO 和所有 T2D 治疗组的 T1D 中显著增加。在所有治疗组的 T2D 小鼠中，非高密度脂蛋白胆固醇（non-HDL-C）显著降低。MSM+SSO 治疗对 HDL 和非高密度脂蛋白胆固醇及 PUFA 代谢的影响，可通过改善血脂谱改善糖尿病患者的临床结局。
