Effects of Egg White Derived Peptides on Metabolic Syndrome Complications: Hypertension, Inflammation, and Insulin resistance

Forough Jahandideh
Metabolic syndrome (MetS), a cluster of several abnormalities of hypertension, inflammation, glucose intolerance and dyslipidemia, enhances a person's risk for cardiovascular disease and type 2 diabetes. The number of people with MetS is increasing largely worldwide. The multifaceted nature of MetS makes patients take several medications to target different aspects of this disease. In addition to significant side effects associated with synthetic drugs and possible drugs interactions, adherence
more » ... ractions, adherence to life-long therapies is usually poor. Therefore, there is increasing interest in developing functional foods or natural health products as an alternative for the prevention and management of the complications of this disease. Bioactive peptides may potentially alleviate several complications of MetS namely hypertension and insulin resistance, the key features of the disease. Several peptides with antioxidant and antihypertensive activity were previously identified from egg white protein ovotransferrin hydrolysate. Egg white contains several proteins including ovotransferrin, therefore, we hypothesized that egg white hydrolysate would have beneficial effects on hypertension, oxidative stress, and inflammation. Moreover, due to the link between hypertension and insulin resistance, egg white hydrolysate may positively affect glucose tolerance and insulin resistance. The main purpose of the current research was to investigate the potential of egg white-derived peptides on hypertension, inflammation, glucose intolerance, and insulin resistance. The specific objectives of this thesis were to 1) evaluate the anti-inflammatory and antioxidant activities of ovotransferrin-derived antioxidant peptides on endothelial cells and their gastrointestinal stability, 2) test the in vivo antihypertensive effect of egg white hydrolysate (EWH) prepared with thermolysin and pepsin with in vitro ACE-inhibitory effect using spontaneously hypertensive rats (SHRs), 3) explore the possible effects of the EWH on adipocyte differentiation v Since EWH is a combination of multiple peptides, we identified the bioactive peptides in EWH with beneficial effects on adipocyte differentiation in 3T3-F442A adipocytes. Our data on the purification and characterization of peptides from EWH with PPARγ stimulatory activity in 3T3-F442A cells identified 42 potent peptides from the major egg white proteins ovalbumin and ovotransferrin. We successfully validated the stimulatory effects of several novel peptide sequences including WEKAFKDED, QAMPFRVTEQE, and VFKGL. ERYPIL was another potent peptide with stimulatory effects on PPARγ expression. For the first time, adipogenic differentiating peptides have been characterized from the hydrolysate of a food-derived protein. Thus, the present study confirmed the effectiveness of EWH on several complications of MetS, including hypertension, inflammation, oxidative stress, glucose tolerance and insulin resistance in vitro and in vivo. We could also identify the bioactive peptides in EWH with beneficial effects on pre-adipocyte differentiation. Findings from this study support the potential of egg proteinderived peptides for uses in the prevention and management of MetS complications. vi PREFACE This thesis contains original work done by Mrs. Forough Jahandideh and has been written according to the guidelines for a paper format thesis of the Faculty of Graduate Studies and Research at the University of Alberta.
doi:10.7939/r3ws8j20d fatcat:6kjxkmamdbfgxmec5lmmavp7jq