Egg white hydrolysate shows insulin mimetic and sensitizing effects in 3T3-F442A pre-adipocytes.

Forough Jahandideh,Sandra T Davidge,Subhadeep Chakrabarti,Jianping Wu,Nobuyuki Takahashi

doi:10.1371/journal.pone.0185653

Forough Jahandideh, Sandra T Davidge + Show 3 more

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https://doi.org/10.1371/journal.pone.0185653

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Abstract

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.

Highlights

Metabolic syndrome, a combination of several abnormalities that increase the risk for type II diabetes and atherosclerosis is global health problem of growing concern [1,2,3]
Adipogenic differentiation in pre-adipocytes is characterized by increases in intracellular lipid droplets and release of adiponectin [35,36]
Treating 3T3-F442A cells with egg white hydrolysate (EWH) for 72 hrs resulted in increased intracellular lipid accumulation as determined by LipidTox staining (Fig 1A)

Summary

Introduction

A combination of several abnormalities that increase the risk for type II diabetes and atherosclerosis is global health problem of growing concern [1,2,3]. Renin angiotensin system (RAS), the classical pathway for controlling blood pressure and fluid balance, has a role in the pathogenesis of metabolic syndrome [5]. Given the role of RAS impairments in the pathogenesis of hypertension and metabolic syndrome, there is much interest in developing novel therapies that can target the common pathologies to hypertension and insulin resistance in more complicated disease conditions [2,8,9]

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