Jahandideh Forough, Chakrabarti Subhadeep, Davidge Sandra T, Wu Jianping
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada.
PLoS One. 2017 Oct 3;12(10):e0185653. doi: 10.1371/journal.pone.0185653. eCollection 2017.
Insulin resistance and inflammation in adipose tissue is a key mechanism underlying metabolic syndrome, a growing health problem characterized by diabetes, obesity and hypertension. Previous work from our research group has demonstrated the potential of egg white ovotransferrin derived bioactive peptides against hypertension, oxidative stress and inflammation in vitro and in vivo. Egg white hydrolysate (EWH) has also shown anti-hypertensive effects in spontaneously hypertensive rats. Given the interplay among hypertension, inflammation, oxidative stress and metabolic syndrome, the objective of the study was to test the EWH on differentiation, insulin signaling and inflammatory responses in 3T3-F442A pre-adipocytes. Our study suggested that EWH could promote adipocyte differentiation as shown by increased lipid accumulation, increased release of adiponectin and upregulation of peroxisome proliferator associated receptor gamma (PPARγ) and CCAAT/ enhancer binding protein alpha (C/EBP-α). In addition to enhanced insulin effects on the upregulation of protein kinase B/Akt phosphorylation, EWH treatment increased extracellular signal regulated kinase 1/2 (ERK1/2) phosphorylation to a level similar to that of insulin, indicating insulin sensitizing and mimetic properties of the EWH. EWH further attenuated cytokine induced inflammatory marker; cyclooxygenase -2 (COX-2) by 48.78%, possibly through the AP-1 pathway by down regulating c-Jun phosphorylation in adipocytes. Given the critical role of adipose in the pathogenesis of insulin resistance and metabolic syndrome, EWH may have potential applications in the prevention and management of metabolic syndrome and its complications.
脂肪组织中的胰岛素抵抗和炎症是代谢综合征潜在的关键机制，代谢综合征是一个日益严重的健康问题，其特征为糖尿病、肥胖症和高血压。我们研究小组之前的工作已经证明，蛋清卵转铁蛋白衍生的生物活性肽在体外和体内具有抗高血压、抗氧化应激和抗炎作用。蛋清水解物（EWH）在自发性高血压大鼠中也显示出抗高血压作用。鉴于高血压、炎症、氧化应激和代谢综合征之间的相互作用，本研究的目的是测试EWH对3T3-F442A前脂肪细胞分化、胰岛素信号传导和炎症反应的影响。我们的研究表明，EWH可以促进脂肪细胞分化，表现为脂质积累增加、脂联素释放增加以及过氧化物酶体增殖物激活受体γ（PPARγ）和CCAAT/增强子结合蛋白α（C/EBP-α）上调。除了增强胰岛素对蛋白激酶B/Akt磷酸化上调的作用外，EWH处理还将细胞外信号调节激酶1/2（ERK1/2）磷酸化增加到与胰岛素相似的水平，表明EWH具有胰岛素增敏和模拟特性。EWH进一步减弱了细胞因子诱导的炎症标志物；环氧合酶-2（COX-2）降低了48.78%，可能是通过下调脂肪细胞中c-Jun磷酸化的AP-1途径。鉴于脂肪在胰岛素抵抗和代谢综合征发病机制中的关键作用，EWH可能在代谢综合征及其并发症的预防和管理中具有潜在应用。
