Department of Biochemistry, Faculty of Natural and Agricultural Science, North West University, Mafikeng Campus, Private Bag X2046, Mmabatho 2735, South Africa.
Department of Biochemistry, Faculty of Science, Adeleke University, Ede 232, P.M.B. 250, Osun State, Nigeria.
Molecules. 2018 Oct 3;23(10):2528. doi: 10.3390/molecules23102528.
Metabolic syndrome, a cluster of different disorders which include diabetes, obesity and cardiovascular diseases, is a global epidemic that is growing at an alarming rate. The origins of disease can be traced back to early developmental stages of life. This has increased mortalities and continues to reduce life expectancies of individuals across the globe. The aim of this study was to investigate the sub-acute and long term effects of neonatal oral administration of oleanolic acid and metformin on lipids (free fatty acids, FFAs) and genes associated with lipid metabolism and glucose transport using a neonatal rat experimental model. In the first study, seven days old pups were randomly grouped into control-distilled water (DW); oleanolic acid (60 mg/kg), metformin (500 mg/kg), high fructose diet (20% /, HF), oleanolic acid (OA) + high fructose diet (OA + HF), and Metformin + high fructose diet (MET + HF) groups. The pups were treated for 7 days, and then terminated on postnatal day (PD) 14. In the second study, rat pups were initially treated similarly to study 1 and weaned onto normal rat chow and plain drinking water on PD 21 till they reached adulthood (PD112). Tissue and blood samples were collected for further analyses. Measurement of the levels of free fatty acids (FFAs) was done using gas chromatography-mass spectrometry. Quantitative polymerase chain reaction (qPCR) was used to analyze the gene expression of , , , , and in the skeletal muscle. The results showed that HF accelerated accumulation of saturated FFAs within skeletal muscles. The HF fed neonatal rats had increased stearic acid, which was associated with decreased glucose, suppressed expression of , , and genes, and increased expression of ( < 0.01) and . OA + HF and MET + HF treated groups had increased mono- and polyunsaturated FFAs; oleic, and octadecadienoic acids than the HF group. These unsaturated FFAs were associated with increased , and ( < 0.01) and decreased and ( < 0.05) in both OA + HF and MET + HF treated groups.
The present study shows that neonatal oral administration of oleanolic acid and metformin potentially protects against the development of fructose-induced metabolic dysfunction in the rats in both short and long time periods.
本研究旨在通过新生大鼠实验模型，研究油酸和二甲双胍对新生大鼠口服给药后脂质（游离脂肪酸，FFAs）和与脂质代谢及葡萄糖转运相关基因的亚急性和长期影响。
在第一研究中，将 7 日龄幼鼠随机分为对照组-蒸馏水（DW）；油酸（60mg/kg），二甲双胍（500mg/kg），高果糖饮食（20%/，HF），油酸（OA）+高果糖饮食（OA+HF）和二甲双胍+高果糖饮食（MET+HF）组。幼鼠处理 7 天，然后在生后第 14 天（PD）处死。在第二研究中，幼鼠最初按研究 1 进行处理，在 PD21 时断奶至正常大鼠饲料和普通饮用水，直至成年（PD112）。收集组织和血液样本进行进一步分析。使用气相色谱-质谱法测量游离脂肪酸（FFAs）水平。采用定量聚合酶链反应（qPCR）分析骨骼肌中 、 、 、 、 和 的基因表达。
HF 加速了骨骼肌中饱和 FFAs 的积累。HF 喂养的新生大鼠的硬脂酸增加，与葡萄糖减少、 、 、 和 基因表达受抑制有关，而 基因表达增加（<0.01）。OA+HF 和 MET+HF 治疗组的单不饱和和多不饱和 FFAs（油酸和十八碳二烯酸）均高于 HF 组。这些不饱和 FFAs 与 OA+HF 和 MET+HF 治疗组的 、 （<0.01）和 、 （<0.05）增加有关。
本研究表明，新生大鼠口服油酸和二甲双胍可在短期和长期内潜在预防果糖诱导的代谢功能障碍的发生。
