Younan Nagat, Elattar Samah, Farouk Mira, Rashed Laila, Estaphan Suzanne
Physiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Histology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Physiol Rep. 2019 Sep;7(17):e14191. doi: 10.14814/phy2.14191.
Menopause increases the risk of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of incretin and/ or exercise on the hepatic fat accumulation in ovariectomized rats. Rats were divided into five groups: Group 1: Control rats, Group 2: Ovariectomized rats, Group 3: Ovariectomized rats + Dipeptidyl peptidase-4 inhibitor (DPPi) (30 mg/kg/day, orally), Group 4: Ovariectomized rats + swimming, and Group 5: Ovariectomized rats + swimming + DPPi. After 6 weeks, Alanine aminotransferase (ALT), glucose, insulin, HOMA IR (Homeostatic Model Assessment for Insulin Resistance), FFA (free fatty acids), Tumor necrosis factor alpha (TNF α), IL6, IL1B levels were measured in blood. The livers were collected for Hematoxylin and eosin (H&E) examination and evaluation of hepatic gene expression of SREBP (sterol regulatory element-binding protein1c), PPAR α (peroxisome proliferator-activated receptor alpha), ACC 1 (acetyl-CoA carboxylase), LC3 (microtubule-associated protein 1 light chain 3), SIRT (sirtuin), hepatic triglycerides, IL6, IL10, caspase 3 and AMPK (adenosine monophosphate-activated protein kinase). A significant increase in ALT level and area of liver tissue defects with a significant increase in glucose HOMA IR, serum FFA, IL6, IL1B, TNF α, liver TGs (triglycerides), inflammation, apoptosis, SREBP1c, ACC1 were found in ovariectomized rats as compared to control group with a significant decrease in PPAR α, LC3, AMPK and SIRT1. DPPi treated rats with and without exercise showed a significant improvement in ALT and area of liver tissue defects, inflammation and apoptosis and serum IL6, IL1B, TNF α, FFA, liver LC3, SIRT1, AMPK, TGs, PPAR α, ACC1 and SREBP1c as compared to the ovariectomized group. Findings from the study confirm the derangement of fat metabolism in the ovariectomized rats and showed that incretin-based therapy and exercise synergistically improved liver fat metabolism, achieved significant beneficial metabolic effects and offer full protection against NAFLD.
绝经会增加非酒精性脂肪性肝病（NAFLD）的风险。我们研究了肠促胰岛素和/或运动对去卵巢大鼠肝脏脂肪堆积的影响。大鼠被分为五组：第1组：对照大鼠；第2组：去卵巢大鼠；第3组：去卵巢大鼠 + 二肽基肽酶 - 4抑制剂（DPPi）（30毫克/千克/天，口服）；第4组：去卵巢大鼠 + 游泳；第5组：去卵巢大鼠 + 游泳 + DPPi。6周后，检测血液中的丙氨酸氨基转移酶（ALT）、葡萄糖、胰岛素、HOMA IR（胰岛素抵抗稳态模型评估）、游离脂肪酸（FFA）、肿瘤坏死因子α（TNFα）、白细胞介素6（IL6）、白细胞介素1β（IL1B）水平。收集肝脏进行苏木精和伊红（H&E）检查，并评估肝脏中固醇调节元件结合蛋白1c（SREBP）、过氧化物酶体增殖物激活受体α（PPARα）、乙酰辅酶A羧化酶1（ACC 1）、微管相关蛋白1轻链3（LC3）、沉默调节蛋白（SIRT）、肝脏甘油三酯、IL6、IL10、半胱天冬酶3和单磷酸腺苷激活蛋白激酶（AMPK）的基因表达。与对照组相比，去卵巢大鼠的ALT水平和肝组织缺陷面积显著增加，同时葡萄糖HOMA IR、血清FFA、IL6、IL1B、TNFα、肝脏甘油三酯（TG）水平、炎症、凋亡以及SREBP1c、ACC1显著升高，而PPARα、LC3、AMPK和SIRT1显著降低。与去卵巢组相比，接受DPPi治疗的大鼠无论是否运动，其ALT和肝组织缺陷面积、炎症和凋亡以及血清IL6、IL1B、TNFα、FFA、肝脏LC3、SIRT1、AMPK、TG、PPARα、ACC1和SREBP1c均有显著改善。该研究结果证实了去卵巢大鼠脂肪代谢紊乱，表明基于肠促胰岛素的治疗和运动可协同改善肝脏脂肪代谢，取得显著有益的代谢效果，并为预防NAFLD提供全面保护。
Zotero 插件
