Nakamura T, Tanimoto H, Mizuno Y, Okamoto M, Takeuchi M, Tsubamoto Y, Noda H
Biological Research Group, Drug Discovery Laboratories Sanwa Kagaku Kenkyusho Inabe-city Mie Japan.
Biopharmaceutical Study Group, Pharmaceutical Research Laboratories Sanwa Kagaku Kenkyusho Inabe-city Mie Japan.
Obes Sci Pract. 2018 Mar 25;4(2):194-203. doi: 10.1002/osp4.164. eCollection 2018 Apr.
Gastric inhibitory polypeptide plays a role in glucose and lipid metabolism and is associated with obesity and insulin resistance. The objective of this study is to confirm the anti-obesity effects of the gastric inhibitory polypeptide receptor antagonist, SKL-14959, on diet-induced obesity mice.
Diet-induced obesity mice at 20 weeks of age were administered with or without SKL-14959 for 96 d. Body weight and food intake were monitored throughout the experiment. Mice were sacrificed, and physiological and biochemical markers were measured, and then histochemical and gene expression analyses were also performed. In further studies, mice were orally gavaged with [C]-oleic acid to investigate the excursion of digested lipids.
SKL-14959 significantly suppressed weight gain without affecting food intake, decreased triacylglycerol contents in the liver and the muscle and the intensity stained with oil-red in the liver. It also improved plasma glutamic pyruvic transaminase and 3-hydroxybutyrate levels in addition to notably down-regulated relative gene expression of srebf1 and dgat1 in the liver despite not altering in the adipose tissue. Furthermore, SKL-14959 showed remarkable inhibition of lipid uptake in the adipose tissue after the oil challenge.
SKL-14959 inhibited lipids uptake and improved lipids metabolism, results in suppression of body-weight gain.
胃抑制多肽在葡萄糖和脂质代谢中起作用，且与肥胖和胰岛素抵抗相关。本研究的目的是证实胃抑制多肽受体拮抗剂SKL-14959对饮食诱导肥胖小鼠的抗肥胖作用。
对20周龄的饮食诱导肥胖小鼠给予或不给予SKL-14959，持续96天。在整个实验过程中监测体重和食物摄入量。处死小鼠，测量生理和生化指标，然后进行组织化学和基因表达分析。在进一步的研究中，给小鼠口服[C]-油酸以研究消化脂质的变化。
SKL-14959显著抑制体重增加而不影响食物摄入量，降低肝脏和肌肉中的三酰甘油含量以及肝脏中油红染色的强度。它还改善了血浆谷丙转氨酶和3-羟基丁酸水平，此外，尽管脂肪组织中未改变，但肝脏中srebf1和dgat1的相对基因表达显著下调。此外，SKL-14959在油刺激后对脂肪组织中的脂质摄取显示出显著抑制作用。
SKL-14959抑制脂质摄取并改善脂质代谢，导致体重增加受到抑制。
