Egg white hydrolysate enhances insulin sensitivity in high-fat diet-induced insulin-resistant rats via Akt activation

Abstract

Agents that block the renin–angiotensin system (RAS) improve glucoregulation in the metabolic syndrome disorder. We evaluated the effects of egg white hydrolysate (EWH), previously shown to modulate the protein abundance of RAS component in vivo, on glucose homeostasis in diet-induced insulin-resistant rats. Sprague–Dawley rats were fed a high-fat diet (HFD) for 6 weeks to induce insulin resistance. They were then randomly divided into four groups receiving HFD or HFD supplemented with different concentrations of EWH (1, 2 and 4 %) for another 6 weeks in the first trial. In the second trial, insulin-resistant rats were divided into two groups receiving only HFD or HFD+4 % EWH for 6 weeks. Glucose homeostasis was assessed by oral glucose tolerance and insulin tolerance tests. Insulin signalling and protein abundance of RAS components, gluconeogenesis enzymes and PPARγ were evaluated in muscle, fat and liver. Adipocyte morphology and inflammatory markers were evaluated. In vivo administration of EWH increased insulin sensitivity, improved oral glucose tolerance (P < 0·0001) and reduced systemic inflammation (P < 0·05). EWH potentiated insulin-induced Akt phosphorylation in muscle (P = 0·0341) and adipose tissue (P = 0·0276), but minimal differences in the protein abundance of tissue RAS components between the EWH and control groups were observed. EWH treatment also reduced adipocyte size (P = 0·0383) and increased PPARγ2 protein abundance (P = 0·0237). EWH treatment yielded positive effects on the inflammatory profile, glucose tolerance, insulin sensitivity and adipocyte differentiation in HFD-induced insulin resistance rats. The involvement of local RAS activity requires further investigation.

A comprehensive review on the glucoregulatory properties of food-derived bioactive peptides

“…Agents that block the renin angiotensin system have shown glucoregulatory potential in the context of metabolic syndrome ( Jahandideh & Wu, 2020 ). The work from our group has shown the insulin sensitizing and mimetic properties of different food-derived antihypertensive peptides ( Chakrabarti et al, 2018 , Jahandideh et al, 2019 , Jahandideh et al, 2017 ). VPP and IPP, the casein-derived tripeptides with well-known antihypertensive properties ( Kim et al, 2008 , Nakamura et al, 2011 ) also enhanced insulin signaling and contributed toward the prevention of insulin resistance in the presence of tumor necrosis factor in 3T3-F442A adipocytes (Chakrabarti, Jahandideh, Liu, & Wu, 2018 ).…”

“…Administration of this protein hydrolysate to insulin resistant rats further increased insulin sensitivity, improved oral glucose tolerance, and reduced systemic inflammation. EWH exhibited its insulin sensitizing effects through potentiating insulin induced Akt phosphorylation in muscle and adipose tissue ( de Campus Zani et al, 2019 , Jahandideh et al, 2019 ).…”

“…Serum adiponectin was enhanced while adipose tissue inflammatory markers were decreased in rats treated with rice protein hydrolysate ( Boonloh et al, 2015 ). We have recently shown the beneficial effects of egg white hydrolysate on adipocyte differentiation and insulin sensitivity in cell culture ( Jahandideh et al, 2017 , Jahandideh et al, 2018 ) and animal studies ( Jahandideh et al, 2019 ). Administration of egg white hydrolysate in insulin resistant rats reduced adipocyte size and increased PPARγ2 protein abundance in the adipose tissue, as well as reduced inflammation in these rats ( Jahandideh et al, 2019 ).…”

Recent findings on the cellular and molecular mechanisms of action of novel food-derived antihypertensive peptides

“…Insulin resistance and by extension, type-2 diabetes have been shown to positively correlate with hypertension and other cardiovascular diseases ( Rojas-Humpire et al, 2021 ). Interestingly, egg white protein hydrolysates have been demonstrated to reduce blood pressure in SHR models ( Jahandideh, Chakrabarti, Davidge, & Wu, 2017 ) and enhance insulin recognition by its receptor in diet-induced insulin resistance in animal model by activating Akt signaling pathway ( Jahandideh et al, 2019 ). This suggests that peptides in the hydrolysates could have upregulated gene expression and enzyme activity of phosphoinositide-dependent protein kinase 1 (IP3K), the enzyme that activates Akt by phosphorylation to enhance insulin sensitivity and the downstream modulation of metabolism that maintains energy and blood pressure homeostasis ( Xing et al, 2019 ).…”

Perspectives on the Potential Benefits of Antihypertensive Peptides towards Metabolic Syndrome

“…Moreover, EWH treatment improved glucose uptake in TNF-α-treated L6 cells by downregulating the activation of p38-mitogen-activated protein kinase (p38) and c-Jun N-terminal kinases (JNK) 1/2 in these cells [140]. Oral administration of EWH to diet-induced insulin resistant rats also reduced adipocyte size, exerted an anti-inflammatory effect, improved glucose tolerance, and enhanced insulin sensitivity in these rats [141]. WEKAFKDED, QAMPFRVTEQE, ERYPIL, and VFKGL were the bioactive peptides responsible for the observed adipogenic differentiating properties of the EWH [142].…”