Food proteins can be considered as source of bioactive peptides that can exert physiological functions to promote health and prevent chronic diseases, such as lipid disorders diabetes, hypertension cancer and obesity which are typical of industrialized societies. Soybean (Glycine max) and white lupin (Lupinus angustifolium) comprise the most widely grown legume crops in the world. In addition to being an invaluable source of oil and proteins for food and feed, many papers from our group pointed out the positive effect of soybean and white lupin proteins on lipid and glucose metabolism. The aim of the present work has been to evaluate in “in vitro” and “in vivo” experiments the ability of soybean and white lupin polypeptides to interact with the molecular mechanisms involved in the regulation of plasma and tissue lipids as well as on the glucose homeostasis. Soybean proteins: the α’ subunit of the soybean 7S globulin, the so called β-conglycinin, was shown to play a key role in the up-regulation of liver high affinity-LDL receptors, in “in vivo” and “in vitro” systems suggesting that biologically active peptides, capable of modulating lipid homeostasis, are likely to be produced by cell and gastrointestinal enzymes. Our research group has been following two different approaches to identify the active peptide/s involved in the lipid regulation. The first one has been to reduce the length of the polypeptide chain of α’ by a biotechnological process obtaining an extension form of α’ chain, roughly covering one third of the full-length polypeptide from N-terminus, which has proved active in the LDL-R up-regulation of Hep G2 cells. The second approach has been to make a screening of peptides with amino acid sequences occurring in α’, α and β subunits of soy β-conglycinin, and test their biological effect “in vitro”. These peptides have been evaluated for their effect on the expression of LDL-receptor, SREBP-2 and HMGCoA red mRNAs in HepG2 cells. Moreover, the peptide that proved more promising among the different compounds under study, has been tested in a rat model of human hypercholesterolemia in order to evaluate its potential on lipid homeostasis. gamma-Conglutin, a lupin seed glycoprotein, plays a key role on the glucose metabolism. Since the “in vitro” interaction of gamma -conglutin with mammalian insulin has been described, in the present study the effect of an oral dose of this protein was studied in an animal model of diabetes in order to evaluate its potential in the fine regulation of glucose homeostasis. Moreover in “in vitro” experiments the ability of gamma-conglutin to interact with cell compartment and to interfere in the insulin pathway has been followed in order to ascertain whether the protein was characterized by insulin-like property. Although the data obtained in this study should be confirmed by human studies, the potential of peptides from α’ subunit of soybean as well as that of lupin seed g-conglutin to control plasma lipids and glycaemia could be considered before developing new therapeutic strategies for the prevention or treatment of lipid/ glucose metabolism disorders.
LEGUME PROTEINS FOR THE MANAGEMENT OF CHRONIC DISEASES:HYPERLIPIDEMIA AND DIABETES / A. Parolari ; tutor: M. Lovati ; coordinator: A. Panerai. - Milano : Università degli studi di Milano. Università degli Studi di Milano, 2014 Dec 16. ((27. ciclo, Anno Accademico 2014.
|Titolo:||LEGUME PROTEINS FOR THE MANAGEMENT OF CHRONIC DISEASES:HYPERLIPIDEMIA AND DIABETES|
|Supervisori e coordinatori interni:||PANERAI, ALBERTO EMILIO|
|Data di pubblicazione:||16-dic-2014|
|Parole Chiave:||glucose metabolism; lipid metabolism; insulin signalling; LDL-R; legume seed;|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Citazione:||LEGUME PROTEINS FOR THE MANAGEMENT OF CHRONIC DISEASES:HYPERLIPIDEMIA AND DIABETES / A. Parolari ; tutor: M. Lovati ; coordinator: A. Panerai. - Milano : Università degli studi di Milano. Università degli Studi di Milano, 2014 Dec 16. ((27. ciclo, Anno Accademico 2014.|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.13130/parolari-anna_phd2014-12-16|
|Appare nelle tipologie:||Tesi di dottorato|