Research ArticleRice bran enzymatic extract restores endothelial function and vascular contractility in obese rats by reducing vascular inflammation and oxidative stress☆
Introduction
Occidental dietary habits have contributed to increased prevalence of obesity, type 2 diabetes mellitus and other pathologies included in the metabolic syndrome [1]. Obesity, in particular abdominal obesity, has been established as a primary contributor to acquired insulin resistance, as increasing adiposity is correlated with impaired insulin action. Endothelial dysfunction, an independent predictor of cardiovascular events [2], has been consistently associated with obesity and the metabolic syndrome [3] in a complex interplay with insulin resistance [4]. Nevertheless, it has been reported that vascular dysfunction of obesity is not only limited to the endothelium but also involves the smooth muscle cell layer, leading to an increased oxidative stress in the vascular wall and the subsequent deregulation of the main control mechanisms providing vascular homeostasis [5]. Vascular function impairment in the metabolic syndrome mainly implies an unbalance between the vasoprotective effect of endothelial nitric oxide (NO) and the unfavorable action of vasoconstrictor factors [e.g., endothelin-1 and reactive oxygen species (ROS)] and proinflammatory mediators [e.g. tumor necrosis factor (TNF)-α] [5]. The pathophysiology of obesity-related vascular dysfunction is therefore an important target for developing new therapeutic approaches aimed to ameliorate cardiovascular risk factors related to metabolic syndrome.
Numerous studies suggest that the first strategy in the prevention of disorders associated with obesity consists of including in the diet food or dietary components with functional properties [6], [7]. Rice, and particularly rice bran, is an excellent nutritional source of bioactive compounds, including high-healthy-value proteins and phytochemicals such as γ-oryzanol, sterols and tocols [8], [9]. Besides, phenolic compounds contained in rice bran, such as γ-oryzanol and ferulic acid, are known to provide strong antioxidant activities [10], [11]. The hypolipidemic, antioxidant and anti-inflammatory properties of the mixture of phytosteryl ferulates contained in γ-oryzanol make it a good candidate for health food [12], [13]. However, the therapeutic use of rice bran is limited because of the insolubility of its proteins and the integrity of its nutraceutical compounds. For this reason, rice bran oils have become commonly utilized in order to study its properties, despite the high risk of rancidity that it involves [14]. These limitations have been counteracted by the recent production of a water-soluble rice bran enzymatic extract (RBEE) [15] that provides numerous advantages over other rice bran derivatives regarding water solubility, increased content in nutraceutical compounds and lack of rancidity.
Our recent investigations have evidenced that a diet supplemented with RBEE is able to ameliorate cardiometabolic risk factors in obese Zucker rats, showing a remarkable action on dyslipidemia, moderate hypertension, insulin resistance and adiponectin levels [16]. However, the effect of RBEE on vascular dysfunction associated with obesity and the main mechanisms by which this rice bran derivative induces its beneficial action on cardiometabolic risk factors remain unknown. The potential of rice bran extracts on vascular alterations has only been recently suggested in a few in vitro investigations which evaluated the effects of γ-oryzanol and a rice bran ethyl acetate extract on adhesion molecules expression in vascular endothelial cells or hypertrophy in smooth muscle cells, respectively [17], [18].
Considering the beneficial effect of an RBEE-enriched diet on cardiometabolic parameters developed in obese rats, it is expected that RBEE will be able to restore endothelial dysfunction and vascular inflammation and oxidative stress associated with obesity in an animal model of metabolic syndrome. Thus, the aim of our study was to determine the capacity of a diet supplemented with RBEE to modify vascular dysfunction in obese Zucker rats and to identify the main pathways that could be implicated in the RBEE bioactivity. Elucidation of these vascular mechanisms might partially explain the beneficial action of RBEE treatment in cardiometabolic parameters of obese animals found in our previous investigations.
Section snippets
Preparation and composition of RBEE
RBEE was prepared according to an enzymatic process previously described [15]. Briefly, RB was modified by enzymatic hydrolysis by using an endoproteases mixture as hydrolytic agent in a bioreactor with controlled temperature (60°C) and pH (pH 8) and using the pH-stat method. The processing of this product follows different steps including centrifugation, filtration and concentration. The final product is brown syrup completely soluble in water. RBEE was chemically characterized by using
Vasodilatation
To evaluate endothelial function, endothelium-dependent vasodilatation to ACh was examined in aortas from the experimental groups. ACh induced concentration-dependent relaxation that was significantly reduced in aortic rings from OC rats compared to lean rats (Fig. 1A). The endothelial dysfunction in OC was also revealed by a lower value of pEC50 (−logEC50) when comparing curves to ACh (pEC50 OC: 7.25±0.06, LC: 7.86±0.24; P<.05), without altering maximal relaxing responses. RBEE significantly
Discussion
Several studies support the beneficial properties of rice bran extracts in cardiometabolic risk factors such as dyslipidemia, hypertension and glucose metabolism [22], [23]. Recent investigations of our group have evidenced the beneficial effects of a novel water-soluble RBEE in vivo on animal models of hypercholesterolemia [24] and metabolic syndrome [16]. Particularly, obese animals fed an RBEE diet showed an important improvement on lipid profile, blood pressure levels, insulin resistance
Acknowledgments
This research was supported by the Spanish Ministry of Science and Innovation (AGL2009-1159). Justo M.L. is a recipient of an FPU fellowship from the Spanish Government. Rodriguez-Rodriguez R. was funded by “Ayudas de movilidad a Profesores Ayudantes Doctores” of the IV Plan Propio de Investigacion (University of Sevilla). Vila E. acknowledges supports from Dirección General de Investigación Científica y Tecnológica (SAF2007-60406). Fluorescence experiments were performed at the “Servei de
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Grants, sponsors and funding sources: This research was supported by The Spanish Ministry of Science and Innovation (AGL2009-1159). Justo M.L. has been a recipient of an FPU fellowship from the Spanish Government.