Elsevier

Nutrition

Volume 30, Issue 4, April 2014, Pages 466-472
Nutrition

Basic nutritional investigation
Rice bran enzymatic extract–supplemented diets modulate adipose tissue inflammation markers in Zucker rats

https://doi.org/10.1016/j.nut.2013.09.016Get rights and content

Abstract

Objective

Chronic low-grade inflammation in obesity is characterized by macrophage accumulation in white adipose tissue and adipokine production deregulation. Obesity also is characterized by oxidative stress related to inflammatory signaling. The aim of this study was to analyze whether dietary supplementation with a rice bran enzymatic extract (RBEE), rich in bioactive compounds with antioxidant and hypocholesterolemic properties, would ameliorate the inflammatory state existing in visceral adipose tissue of obese Zucker rats.

Methods

Obese Zucker rats and their littermate controls, lean Zucker rats ages 8 wk, were daily fed an enriched diet with either 1% or 5% RBEE supplementation over 20 wk. Measurement of adipocyte size and mRNA expression of proinflammatory molecules from visceral abdominal/epididymal tissue was performed.

Results

An RBEE-supplemented diet decreased the overproduction of tumor necrosis factor-α, interleukin (IL)-6, IL-1 β, and inducible nitric oxide synthase (iNOS), as well as the overproduction of IL-6 and iNOs in visceral abdominal adipose tissue and visceral epididymal adipose tissue, respectively. An RBEE-supplemented diet modified the adipocyte-size distribution pattern in both abdominal and epididymal adipose tissue, shifting it toward smaller cell sizes.

Conclusions

Chronic administration of a novel water-soluble RBEE, rich in polyphenols, tocotrienols and γ-oryzanol, could be a suitable treatment to ameliorate the obesity-associated proinflammatory response.

Introduction

Obesity is characterized by a chronic and systemic low-grade inflammation in adipose tissue that is believed to contribute to the development of insulin resistance (IR) leading to type 2 diabetes and is also a risk factor for cardiovascular diseases (CVDs). This hypothesis has gradually replaced the idea of considering adipose tissue as a simple energy store but also as an endocrine organ that secretes a number of bioactive peptides collectively named adipokines, which are relevant at the interface between the immune and the metabolic systems [1]. The adipose organ includes numerous discrete anatomical depots and although subcutaneous adipose tissues store > 80% of total body, visceral adipose tissue have been shown to correlate better with metabolic syndrome and IR than subcutaneous fat depots [2]. Also, the expression of proinflammatory cytokines is generally higher in visceral than in subcutaneous fat [3], [4]. Adipose tissue contains adipocytes as well as fibroblasts, preadipocytes, tissue-resident macrophages, and vascular constituents, being macrophages crucial contributors to inflammation. In fact, inflammation in adipose tissue is partially due to an influx of macrophages that secrete proinflammatory factors like tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1 beta (IL-1 β) and inducible nitric oxide synthase (iNOS) [5], [6], [7], [8]. It is known that in obesity there is a remarkable shift in the pool of tissue macrophages from the alternatively activated M2 type to the classically activated M1 type, changing the secretion of cytokines from predominantly anti-inflammatory (M2) to proinflammatory (M1) [9]. In addition to macrophages, adipocytes also secrete specific cytokines, such as adiponectin and leptin. Adiponectin possesses anti-inflammatory effects and serum levels are markedly decreased in patients with visceral obesity and states of IR such as type 2 diabetes. [1].

Zucker rats have a point mutation resulting in dysfunctional leptin receptors that makes them leptin-insensitive, leading to an altered leptin metabolism and obesity. Thus, these rats are obese, normoglycemic, insulin-resistant, hyperinsulinemic, hypertriglyceridemic, and hypercholesterolemic. Accordingly, the Zucker rat represents an appropriate model for studying the effect of dietary components on factors associated with metabolic disturbances in overweight. Additionally, obese Zucker rats develop a proinflammatory response and oxidative stress [10]. In this context, TNF-α, a proinflammatory cytokine, is overexpressed in obesity and likely mediates IR in animal models of obesity including obese Zucker rats [5], [11].

Rice bran, a byproduct of rice milling, is an important source of bioactive molecules of particular interest as an antioxidant and a lipid-lowering compound, including γ-oryzanol, tocols (tocopherols and tocotrienols), and unsaturated fatty acids [12], [13]. Although rice bran shows an important composition in natural antioxidants and nutritional proteins [12], [14], its potential use as a functional food is limited by the high insolubility of its protein, as well as the integrity of its nutraceutical components, particularly referring to the phenolic fraction. Our group has developed a new product from rice bran, a water-soluble rice bran enzymatic extract (RBEE), which preserves functional properties and improves solubility of proteins and the antioxidant components of rice bran [15]. The enzymatic treatment also increases concentration of minor functional components making our RBEE rich in bioactive compounds as polyphenols, fitosterols, and amino acids with antioxidant [16] and hypocholesterolemic activity [17]. Previous results have already demonstrated that an RBEE-enriched standard diet ameliorated metabolic parameters related to IR and CVD in obese Zucker rats [18], [19]. In the light of these data, the main goal of the present study was to investigate the ability of RBEE to prevent the inflammation state present in adipose tissue in obesity, focusing on the putative modulator effects of rice bran extract on cytokine expression in visceral adipose tissue.

Section snippets

Animals and diets

Obese Zucker (OBZ) rats and their littermate controls, lean Zucker (LZ) rats (8 wk old, Charles River Laboratories, Barcelona, Spain) were fed a standard diet and water ad libitum. OBZ rats were divided into two groups and daily treated with either 1% RBEE supplementation (OBZ1) or 5% RBEE supplementation (OBZ5). Treatment with RBEE was administered over 20 wk as a syrup form included in a standard diet, supplemented with the concentrations indicated above.

RBEE, extracted as previously

Body weight and weight of visceral adipose fat

The increase in body weight in OBZ rats was significantly higher (P < 0.001) than LZ littermates during the treatment (Table 1). Treatment with RBEE lowered slightly this increases in both groups (OBZ1 and OBZ5).

The weight of abdominal and epididymal fat tissue are evaluated for all experimental groups and are summarized in Table 1. Treatment with RBEE did not alter significantly fat weight in OBZ rats. Only weight of VAT in rats fed a 5% RBEE diet was significantly reduced compared with

Discussion

The purpose of this study was to investigate the effect of a new water-soluble RBEE on inflammatory markers in OBZ rats. Although no significant differences were observed in the final body weight and in the adipose tissue weight between the different groups, RBEE-enriched diets were able to modulate the altered production of cytokines, characteristic of adipose tissue in OBZ rats, and also modified the adipocyte size distribution pattern in both VAT and VET shifting it toward smaller cell sizes.

Conclusions

In summary, our present work demonstrates that chronic administration of a novel water-soluble RBEE could be a suitable treatment to ameliorate the obesity-associated proinflammatory response. Our results provide evidence of the nutraceutical properties of RBEE against the pathogenesis of obesity and reinforce the potential of RBEE as a functional food.

Acknowledgments

This research was supported by The Spanish Ministry of Science and Innovation (AGL2009-1159). ML Justo has been a recipient of an FPU fellowship from the Spanish Government. The authors acknowledge the Enzymatic Production Technology Group of University of Seville (Spain) for supplying the drug for this study.

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    MC and MLJ contributed equally to this work. RR-R and MDH conceived and designed the study. MLJ and MC carried out the experiments. AC conceived the experiments and analyzed the data. All authors were involved in writing the paper and had final approval of the submitted and published versions. The authors declared no conflicts of interest.

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