Dumeus Stanley, Shibu Marthandam Asokan, Lin Wan-Teng, Wang Ming-Fu, Lai Chao-Hung, Shen Chia-Yao, Lin Yueh-Min, Viswanadha Vijaya Padma, Kuo Wei-Wen, Huang Chih-Yang
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Department of Medicine, State University of Haiti, Faculty of Medicine and Pharmacy, Port-au-Prince, Haiti.
Cell Physiol Biochem. 2018;48(5):1942-1952. doi: 10.1159/000492518. Epub 2018 Aug 9.
BACKGROUND/AIMS: High-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) poses therapeutic challenges in elderly subjects. Due to lack of efficient drug therapy, plant-based bioactive peptides have been studied as alternative strategy in NAFLD and for less toxicity in elderly. To mimic fatty liver in aging conditions, researchers highly commended the genetically engineered strains SAMP8 (senescence-accelerated mice prone 8). However, there is a paucity of reports about the anti-steatosis effects of bioactive peptides against fatty liver development under a combined action of high-fat diet exposure and aging process. This study was conducted to evaluate the activity of DIKTNKPVIF peptide synthesized from alcalase-generated potato protein hydrolysate (PH), on reducing HFD-driven and steatosis-associated proinflammatory reaction in ageing model.
Five groups of six-month-old SAMP8 mice (n=4, each) were fed either a normal chow (NC group) for 14 weeks upon sacrifice, or induced with a 6-week HFD feeding, then treated without (HCO group) or with an 8-week simultaneous administration of peptide (HPEP group), protein (HPH group) or probucol (HRX group). Liver organs were harvested from each group for histological analysis and immunoblot assay.
In contrast to NC, extensive fat accumulation was visualized in the liver slides of HCO. Following the trends of orally administered PH, intraperitoneally injected peptide reduces hepatic fat deposition and causes at protein level, a significant decrease in HFD-induced proinflammatory mediators p-p38 MAPK, FGF-2, TNF-α, IL-6 with concomitant reactivation of AMPK. However, p-Foxo1 and PPAR-α levels were slightly changed.
Oral supplementation of PH and intraperitoneal injection of derived bioactive peptide alleviate proinflammatory reaction associated with hepatosteatosis development in elderly subjects, through activation of AMPK.
背景/目的：高脂饮食（HFD）诱导的非酒精性脂肪性肝病（NAFLD）给老年患者带来了治疗挑战。由于缺乏有效的药物治疗，基于植物的生物活性肽已被研究作为NAFLD的替代策略，且对老年人毒性较小。为了模拟衰老条件下的脂肪肝，研究人员高度推荐基因工程菌株SAMP8（易患衰老加速小鼠8）。然而，关于生物活性肽在高脂饮食暴露和衰老过程共同作用下对脂肪肝发展的抗脂肪变性作用的报道较少。本研究旨在评估由碱性蛋白酶水解马铃薯蛋白产生的DIKTNKPVIF肽对衰老模型中HFD驱动的和与脂肪变性相关的促炎反应的抑制活性。
将五组六个月大的SAMP8小鼠（每组n = 4）在处死前14周喂食普通饲料（NC组），或进行为期6周的HFD喂养，然后不进行处理（HCO组）或同时进行为期8周的肽（HPEP组）、蛋白质（HPH组）或普罗布考（HRX组）给药。从每组中采集肝脏器官进行组织学分析和免疫印迹测定。
与NC组相比，HCO组肝脏切片中可见广泛的脂肪堆积。遵循口服PH的趋势，腹腔注射肽可减少肝脏脂肪沉积，并在蛋白质水平上导致HFD诱导的促炎介质p-p38 MAPK、FGF-2、TNF-α、IL-6显著降低，同时伴随AMPK的重新激活。然而，p-Foxo1和PPAR-α水平略有变化。
口服补充PH和腹腔注射衍生的生物活性肽可通过激活AMPK减轻老年患者与肝脂肪变性发展相关的促炎反应。
