Impact of Wheat Aleurone Structure on Metabolic Disorders Caused

Article pubs.acs.org/JAFC

Impact of Wheat Aleurone Structure on Metabolic Disorders Caused by a High-Fat Diet in Mice Natalia Nicole Rosa,†,‡ Jenna Pekkinen,‡ Karla Zavala,‡ Gilles Fouret,§ Ayhan Korkmaz,∥ Christine Feillet-Coudray,§ Mustafa Atalay,∥ Kati Hanhineva,‡ Hannu Mykkan̈ en,‡ Kaisa Poutanen,‡,⊥ and Valérie Micard*,†,‡ †

Montpellier SupAgro-INRA-UMII-CIRAD, JRU IATE1208 Agropolymers Engineering and Emerging Technologies, 2 Place Pierre Viala, F-34060 Montpellier, France ‡ Institute of Public Health and Clinical Nutrition, Food and Health Research Centre, University of Eastern Finland, P. O. Box 1627, FIN-70211 Kuopio, Finland § UMR 866 Dynamique Musculaire et Métabolisme, INRA, 2 Place Pierre Viala, 34060 Montpellier Cedex 1, France ∥ Institute of Biomedicine, Physiology, University of Eastern Finland, P. O. Box 1627, FIN-70211 Kuopio, Finland ⊥ VTT Technical Research Centre of Finland, P. O. Box 1000, FI-02044 Espoo, Finland S Supporting Information *

ABSTRACT: The present study investigated the potential of native and structurally modified wheat aleurone, by dry-grinding or enzymatic treatments, to counteract metabolic disorders in mice with diet-induced obesity (DIO). C57BL6/J mice were first fed ad libitum with a high-fat diet for 9 weeks to induce obesity, after which the native or treated aleurone fractions were added (13% (w/w)) in the high-fat diets for an additional 8 weeks. The effects of the aleurone-enriched diets were evaluated by assessing body weight gain, adiposity, fasting blood glucose, plasma insulin and leptin, and anti-inflammatory and oxidative stress markers. Enrichment of the diet with native or finely ground aleurone did not improve any parameter analyzed; finely ground aleurone even slightly increased (p = 0.03) body weight gain. Enrichment of the diet with enzymatically treated aleurone only had a tendency toward lower body weight gain, visceral adipose tissue accumulation, fasting plasma insulin, and leptin levels. KEYWORDS: aleurone, enzymatic treatment, grinding, obesity, oxidative stress

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The dietary fibers in the cell walls of aleurone consist mainly of insoluble arabinoxylan (AX), and to a lesser extent β-glucans. AX fibers are highly esterified with phenolic acids,8 the most abundant being ferulic acid (FA) monomer, followed by minor amounts of dimeric FA, sinapic acid, and p-coumaric acid.9 Some studies have demonstrated various health effects of purified wheat AX in humans10,11 and alleviation of obesity and improvement in insulin resistance in mice.12 Free FA has a welldocumented antioxidant property in vitro suggested as beneficial for the treatment of disorders linked to oxidative stress although it is still not clear if a reasonable dietary intake would be adequate to generate biological effects.13 Taken together, the beneficial effects of free FA and AX are wellknown, but only a few studies have evaluated potential health effects of wheat aleurone in vivo. Wheat aleurone was effective for decreasing levels of IL-6 of obese mice,14 reducing the risks of hypertension and hyperglycemia in obese spontaneously hypertensive rats15 and lowering plasma concentrations of the inflammatory marker C-reactive protein in humans.16 In order to increase the nutritional potential of wheat aleurone and bran fractions, some researchers have used dry

INTRODUCTION

Obesity can be defined as an increase in body weight resulting from excessive fat accumulation mainly in the adipose tissue after prolonged positive energy balance. It is a well-established risk factor for type 2 diabetes, cardiovascular diseases, and metabolic syndrome (a constellation of metabolic disturbances such as dyslipidemia, abdominal obesity, insulin resistance, inflammation, and hypertension).1 Furthermore, obesity is considered a low-intensity chronic inflammation, which can contribute in various ways to elevated oxidative stress levels seen in obese human subjects.2 Increased oxidative stress in obesity, i.e., an imbalance between free radicals and antioxidant defenses, could be lowered by physical activity, dietary restriction, and diets rich in antioxidants.2 Studies conducted on humans indicate that higher intakes of whole-grain products are associated with a lower adiposity3 or reduction of the body weight gain.4 Wheat grains are rich in fibers, vitamins, minerals, and phytochemicals (especially phenolic compounds), which have been suggested as important contributors to their physiological effects.5 In the wheat grain, these bioactive compounds are concentrated in the peripheral layers (technological fraction known as bran), especially in aleurone, a unicellular layer located between the endosperm and the outer layers.6 Wheat aleurone can be isolated from the other bran layers through novel dry-fractionation techniques.7 © 2014 American Chemical Society

Received: Revised: Accepted: Published: 10101

July 14, 2014 September 17, 2014 September 19, 2014 September 19, 2014 dx.doi.org/10.1021/jf503314a | J. Agric. Food Chem. 2014, 62, 10101−10109

Journal of Agricultural and Food Chemistry

Article

Figure 1. Experimental design of this study. Low-fat diet was provided during the whole period to the LFD group. High-fat diet was provided to the other groups during the first period (9 weeks), and during the second period (8 weeks) the diet was switched to the following diets: low-fat (HFD + LFD group), high-fat (HFD group), native aleurone (A-N group), ground aleurone (A-G group), xylanase treated aleurone (A-XYN group), xylanase and feruloyl esterase treated aleurone (A-XYNFAE), or commercial ferulic acid (C-FA group). Midpoint groups received either high-fat (HFD1/2) or low-fat (LFD1/2) diets and were sacrificed in the end of the first period (9 weeks).

Table 1. Composition of the Diets: Carbohydrate, Fat, Protein, Cellulose, Mineral, Vitamin, Arabinoxylans (AX; Total, Insoluble, and Soluble), and Ferulic Acid (FA; Bound, Conjugated, and Free) Expressed as grams per 100 ga control diets carbohydrate fat protein cellulose mineral mix vitamin mix total AX insoluble AX soluble AX total FA bound FA conjugated FA free FA antioxidant capacity

aleurone diets

HFD

LFD

41.4 23.6 23.7 5.0 1.0 1.0 0.52 ± 0.01 0.49 ± 0.01 0.03 ± 0.00 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 10.7 ± 1.0

67.3 4.3 19.2 5.0 1.0 1.0 0.42 ± 0.00 0.39 ± 0.00 0.03 ± 0.00 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 0.0 ± 0.0 10.8 ± 0.8

A-N 39.5 22.5 22.5 0.0 1.0 1.0 3.80 3.61 0.19 0.11 0.10 0.00 0.00 14.1

± ± ± ± ± ± ± ±

A-G

0.01 0.02 0.02 0.0 0.0 0.0 0.0 0.6

39.3 22.4 22.4 0.0 1.0 1.0 3.88 3.63 0.25 0.11 0.11 0.01 0.00 15.1

± ± ± ± ± ± ± ±

0.15 0.16 0.02 0.0 0.0 0.0 0.0 2.0

FA diet

A-XYN 39.7 22.6 22.7 0.0 1.0 1.0 3.75 2.28 1.47 0.09 0.05 0.03 0.01 22.9

± ± ± ± ± ± ± ±

0.07 0.08 0.03 0.0 0.0 0.0 0.0 4.0

A-XYNFAE 39.5 22.5 22.6 0.0 1.0 1.0 3.42 0.84 2.58 0.07 0.01 0.02 0.04 27.5

± ± ± ± ± ± ± ±

0.2 0.27 0.15 0.04 0.06 0.03 0.01 3.1

C-FA 41.4 23.6 23.7 5.0 1.0 1.0 0.57 0.54 0.03 0.10 0.00 0.01 0.08 25.9

± ± ± ± ± ± ± ±

0.03 0.03 0.00 0.04 0.00 0.02 0.00 1.4

a The antioxidant capacity is expressed as mmol of TEAC/kg. Arabinoxylans, ferulic acid contents, and antioxidant capacity are reported as means ± SD. Amounts of carbohydrate, fat, protein, minerals, and vitamins in aleurone diets were added to match the energy content similar to that of the high-fat diet. For HFD-, A-N-, A-G-, A-XYN-, A-XYNFAE-, and C-FA-enriched diets: carbohydrate = corn starch (21%), maltodextrin (29%), and sucrose (50%); fat = soybean oil (12.3%) and lard (87.7%); protein = casein (98.5%) and L-cystine (1.5%). For LFD: carbohydrate = corn starch (45%), maltodextrin (5%), and sucrose (50%); fat = soybean oil (55.6%) and lard (44.4%); protein = casein (98.5%) and L-cystine (1.5%).

improved to a larger extent its antioxidant capacity19 and also allowed greater and faster metabolism of FA in an in vitro gut fermentation model.20 Bioprocessed wheat bran had higher bioavailability of its phenolics in vitro and ex vivo.23,24 The aim of this work was to investigate the capacity of differently processed wheat aleurone fractions (native, finely ground, or enzymatically treated) to counteract metabolic disorders in a diet-induced-obesity mouse model. The design of this study consisted of first inducing obesity in mice (first

and wet processes to increase the bioaccessibility and bioavailability of bioactive compounds. Ultrafine dry grinding of the wheat bran and aleurone layer improved indeed their antioxidant capacity and fermentability and increased the bioavailability of their phenolic compounds.17−21 The inner part of aleurone obtained by debranning and air classification also presented higher bioaccessibility of phenolic compounds and vitamins compared to the outer part of aleurone or the unfractionated bran.22 Enzymatic treatment of aleurone 10102

dx.doi.org/10.1021/jf503314a | J. Agric. Food Chem. 2014, 62, 10101−10109


Article

12 h/12 h light/dark cycle with lights on at 7 am. The experimental design is showed in Figure 1. After 1 week of acclimatization, mice (n = 85) were fed ad libitum a commercial high-fat diet (D12451, Research Diets) for 9 weeks to induce obesity and related metabolic disorders. The control group (n = 20) was fed ad libitum a commercial low-fat control diet (D12450B, Research Diets). After 9 weeks of prefeeding, 10 mice receiving high-fat diet and 10 mice receiving lowfat diet were sacrificed (midpoint groups HFD1/2 and LFD1/2). These midpoint groups were used in order to evaluate the metabolic status of mice in the end of the first period. The rest of the mice receiving high-fat diets were randomized into 7 study groups (n = 9− 14 per group) and were fed either with D12451 (high-fat diet control, HFD, n = 14), D12450B (group switched from high- to low-fat diet, named as lifestyle control group HFD + LFD, n = 9), the D12451 diets enriched with aleurone fractions (A-N, A-G, A-XYN, and AXYNFAE diets, n = 10, 11, 10, and 11, respectively) or commercial ferulic acid (C-FA diet, n = 11) for 8 weeks. The group receiving the low-fat diet (LFD, n = 10) remained on the same diet until the end of the study to serve as a “healthy control”. The lifestyle control group (HFD + LFD) was used in order to compare the effects of the consumption of aleurone-enriched diets with a energy-restricted diet. At the end of the experiment, the mice were fasted for 7.5−8.5 h and sacrificed by decapitation after being made unconscious by CO2 gas. Venous blood was collected into ethylenediametetraacetic acid (EDTA) tubes (K2-EDTA Microtainer Tubes with BD Microgard Closure, Beckton Dickinson Oy) and centrifuged for 10 min × 16000g at room temperature. Plasma was frozen on dry ice and stored at −70 °C in smaller aliquots. Tissues including liver were dissected immediately after blood collection, rinsed with physiological saline, wrapped into aluminum foil, snap frozen in liquid nitrogen, and stored at −70 °C until further processing. The animal experiments were approved by the Institutional Animal Care and Use Committee of the Provincial Government of Finland (permission no. 041003). Monitoring of the Body Weight and Feed Intake. The body weight of the mice was measured weekly. Feed intake was also monitored weekly (always on the same day of the week) by determining the difference between the pellets supplied and the amount of pellets left on the grid and taking the spillage of the pellets into account. The energy intake was calculated based on the feed intake and the energy density of the diet. The average feed intake was calculated based on the diet consumption of each mouse during the first (weeks 1−9) and second (weeks 10−17) periods of the experiment. Assays of Plasma Samples. Blood glucose was measured by LifeScan OneTouch Ultra glucometer from the venous blood drops immediately after decapitation. The following analyses were performed in the frozen plasma which was thawed just before carrying out the experiments. C-reactive protein (CRP), pro-inflammatory cytokines (IL-6 and IL-1β), anti-inflammatory cytokines (IL-10), tumor necrosis factors α (TNFα), leptin, and insulin were measured from the plasma using Multiplex Biomarker Immunoassays for Luminex xMAP technology (Millipore, Billerica, MA, USA) following the instructions of the manufacturer. The CRP was assessed by MAP2MAG-76K kit; cytokines IL-1β, IL-6, IL-10, and TNFα were measured by MCYTOMAG-70K kit, and leptin together with insulin, by MMHMAG-44K-02 kit. For measurement of the cytokines, the lowest concentration of the calibration curve was 3.2 mg/L. However, some plasma samples presented concentrations under this limit of detection, and an arbitrary medium value of 1.6 mg/L was attributed to them. Measurement of Liver Oxidative Stress Markers. Livers were cryo-ground in 10 mL grinding steel jars with a stainless steel ball for 60 s with 15 Hz using TissueLyser II (Qiagen). The obtained liver powder was used for the oxidative stress marker analyses. The amounts of total (TGSH) and oxidized (GSSG) gluthathione were determined spectrophotometrically as described previously.25 Lipid peroxidation level was evaluated by thiobarbituric acid−reactive substances (TBARS) and lipid hydroperoxydes (LPO), which were measured according to the method of Sunderman et al.26 and Kinnunen et al.,27 respectively. Sulfhydryl groups (SH) was measured according to Faure and Lafond28 and protein carbonyls using the ELISA method as

period, 9 weeks fed with high-fat diet) and then providing the processed aleurone fractions (second period −8 weeks fed with high-fat diet enriched with aleurone) (Figure 1). The aleurone was added in the diet of mice in order to provide 5% of the dietary fiber, which is a common level used in mice studies. Besides aleurone-enriched diets, high- and low-fat diets without aleurone were also provided during the whole experiment (first + second periods) as two control groups. The effects of the different aleurone-enriched diets were evaluated by recording obesity (body weight gain, adiposity), fasting blood glucose, fasting plasma insulin and leptin, pro- and anti-inflammation markers, and oxidative stress.

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MATERIALS AND METHODS

Wheat Aleurone Layer Treatments. The native aleurone-rich fraction (85% aleurone) was obtained by dry processing of bran provided by Bühler AG (Uzwil, Switzerland). Its chemical composition is described by Rosa et al.19 (39.7 g of dietary fiber, 22.2 g of protein, 13.3 g of ash, 9.8 g of fat, and 5.8 g of starch in 100 g of wheat aleurone dry matter). The native aleurone had 192 μm mean particle size (d50) and 24.3 and 0.6 g of total AX and total FA/(100 g), respectively. AX of native aleurone was present mainly in insoluble form (96.3%), and FA was mainly esterified to polysaccharides (98.5%). Three treatments were applied on the native aleurone to obtain three modified aleurone fractions: (i) finely ground aleurone, (ii) xylanase treated aleurone, and (iii) xylanase and feruloyl esterase treated aleurone.20 The finely ground aleurone, which was obtained by ultrafine grinding with an impact mill in cryogenic conditions, had 65 μm mean particle size. The finely ground aleurone had amounts of insoluble AX and bound FA similar to that of the native one. Both enzymatic treated aleurones had amounts of total AX and total FA similar to that the native aleurone, but the proportions of soluble AX and free FA were higher in these treated fractions. The aleurone fractions were prepared in UMR IATE (Montpellier, France), and their total composition was described in our previous work.20 Study Diets. Each aleurone fraction was added at concentration 13% (w/w) in a commercial high-fat diet with 45% of energy from fat (D12451 high-fat diet; Research Diets Inc., New Brunswick, NJ, USA). High-fat diet ingredients and aleurone fraction were mixed and then extruded into pellets using a cold extrusion process. The pellets were manufactured by Research Diets. The total composition of each pellet is displayed in Table 1. Pellets will be called diet throughout this work. Based on the initial chemical composition of native aleurone, all of the aleurone-enriched diets were designed to match the commercial highfat diet with calorie density, the amount of macronutrients, and the total fiber content (5%). The diets and study groups receiving the aleurone fractions, native, finely ground, xylanase treated, and xylanase plus feruloyl esterase treated, were named as A-N, A-G, A-XYN and AXYNFAE, respectively. Commercial FA (Sigma, St. Louis, MO, USA) was also added into the high-fat diet (named as group C-FA) in the same concentration as the FA content of the AN diet. Phenolic acids (bound to polysaccharides, conjugated to mono- or oligosaccharides, and in the free form) and AX (insoluble and soluble forms) contents were determined in the pellets after the addition of aleurone fractions in order to check that these compounds were not lost or deconjugated during the extrusion process and to measure the exact amount of AX and FA consumed by mice in each diet. The total antioxidant capacity of the pellets was also determined. All of the methodologies used are described by Rosa et al.18,20 The pellets were stocked into bags under vacuum at 4 °C and protected from light to avoid oxidation during the experiment. Animals and Experimental Design. C57BL/6J male mice were obtained from the National Laboratory Animal Center (Kuopio, Finland) at the age of 9 weeks (initial weight = 23.8 ± 0.2 g). The mice were acclimatized for 1 week and housed 3−4 animals per cage during the weeks 1−12 and in single cages from week 13 until the end of the study (week 17). The conditions in the animal house were controlled: temperature, 22 ± 1 °C; relative air humidity, 55 ± 15%; 10103



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Figure 2. (A) Development of body weights of mice during the first (9 weeks) and second (8 weeks) periods. (B) Body weight gain during the second period (weeks 10−17). Weights for subcutaneous (C) and visceral (D) adipose tissues (percent body weight) at the end of the experiment (week 17). The values are reported as means ± SEM (n = 10, 9, 14, 10, 11, 10, 11, and 11 for LFD, HFD + LFD, HFD, A-N, A-G, A-XYN, AXYNFAE, and C-FA, respectively). Values not significantly different (p > 0.05) are designated by pairs of letters. previously described by Oksala et al.29 Oxygen radical absorbance capacity (ORAC) was used for the measurement of the antioxidant capacity, which was performed using a multiwell plate reader according to the methods described previously.30 The activity of antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) was measured according to the method of Beers and Sizer,31 Flohe and Gunzler,32 and Marklund,33 respectively. Protein carbonyls and ORAC measurements were performed in triplicate, and the other markers were measured in duplicates. Statistical Analysis. Results were expressed as means ± standard error of the mean (SEM). Statistical analysis based on one-way ANOVA was applied followed by a Tukey−Kramer honest significant difference (HSD) posthoc test at 95% confidence level (p < 0.05) for the data following a normal distribution and having similar variance. The student’s t-test at 95% confidence level (p < 0.05) was also applied in pairs between the HFD control group and each aleuroneenriched group. Correlation analyses were carried out by the Pearson’s correlation method with a 95% confidence interval. For the analysis of the midpoint groups (HFD1/2 and LFD1/2), the student’s t-test (p < 0.05) was applied.

and A-XYNFAE had higher proportion of AX in soluble form (39 and 75%, respectively). The total amount of FA in the aleurone-enriched diets was around 0.07−0.1 g/(100 g), which was equivalent to the amount of commercial FA in the C-FA diet (0.1 g/(100 g), mainly in free form). Both diets A-N and A-G had 95% of FA as bound to AX polysaccharides (Table 1). A-XYN and A-XYNFAE diets contained higher amounts of FA in both conjugated and free forms (41 and 84% for A-XYN and A-XYNFAE, respectively). The controls (HFD and LFD) and C-FA diets contained traces of AX, which came from the cellulose fraction added in these diets. Any traces of FA were detected in the control diets. The antioxidant capacity of the diets was measured and expressed in Trolox equivalent antioxidant capacity (TEAC). HFD and LFD had similar antioxidant capacity (10.8 mmol of TEAC/kg). Enrichment of the diets with either enzymatically treated aleurone fractions (A-XYN and A-XYNFAE diets) or free FA (C-FA diet) clearly increased the antioxidant capacity of the high-fat diets (2.5- and 2.1-fold for A-XYN and A-XYNFAE diets, respectively; Table 1). The diets A-N and A-G had slightly higher antioxidant capacity (1.3- and 1.4-fold, respectively) as compared to HFD alone (Table 1). Metabolic Status after 9 week High-Fat Feeding. The high-fat diet resulted in significantly (p < 0.05) higher body weight after 9 weeks of feeding (31.4 ± 0.9 vs 28.2 ± 0.4 g for HFD1/2 and LFD1/2 groups, respectively; see the Supporting

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RESULTS Characterization of the Aleurone-Enriched Diets. The total amounts of AX in the aleurone-enriched diets (A-N, A-G, A-XYN, and A-XYNFAE) were around 3.4−3.9 g/(100 g) (Table 1). Both diets A-N and A-G contained AX mainly in insoluble form (95%). The enzymatic process applied on aleurone efficiently solubilized AX, and thus the diets A-XYN 10104



10105

a

Food intake and energy intake are the average consumption during the second period. The values are reported as means ± SEM. The values not significantly different (p > 0.05) are designated by the same letter.

36.0 ± 1.5abc 3.17 ± 0.06cd 14.5 ± 0.2abc 1.07 ± 0.04a 0.089 ± 0.01a 0.17 ± 0.01a 9.9 ± 0.4aa 37.9 ± 1.0ab 3.38 ± 0.07bcd 15.5 ± 0.3ab 0.98 ± 0.06ab 0.086 ± 0.01ab 0.17 ± 0.01a 10.5 ± 0.9a 40.5 ± 1.7a 3.25 ± 0.07cd 14.6 ± 0.2abc 0.96 ± 0.07abc 0.079 ± 0.0ab 0.17 ± 0.01a 10.4 ± 0.7a 39.0 ± 1.7ab 3.43 ± 0.08abc 15.4 ± 0.3ab 0.96 ± 0.05abc 0.088 ± 0.01ab 0.17 ± 0.01a 10.9 ± 0.6a 37.4 ± 1.2ab 3.33 ± 0.06cd 15.5 ± 0.3a 0.77 ± 0.05bc 0.064 ± 0.00ab 0.15 ± 0.01a 10.2 ± 0.5a 32.7 ± 0.5bc 3.62 ± 0.08ab 13.9 ± 0.3c 0.89 ± 0.05abc 0.077 ± 0.01ab 0.15 ± 0.01a 9.0 ± 0.5a 31.3 ± 0.5c 3.69 ± 0.07a 14.2 ± 0.3bc 0.85 ± 0.05abc 0.091 ± 0.01a 0.17 ± 0.01a 8.1 ± 0.6a final body weight (g) food intake (g/day) energy intake (kcal/day) intestinal tissue (g) cecum tissue (g) colon tissue (g) glucose (mmol/L)

A-XYNFAE A-XYN A-G A-N HFD HFD + LFD LFD

Table 2. Body Weight, Weights of Intestinal, Caecum, and Colon Tissues, and Fasting Plasma Glucose of Mice in the End of the Second Perioda

C-FA

Information Table S1). The adiposity index, i.e., the amount of adipose tissue (subcutaneous and visceral) in relation to the body weight, was significantly (p < 0.05) higher in the HFD1/2 group (4.8 vs 2.6% for HFD1/2 and LFD1/2, respectively) at the end of the first period. The plasma fasting insulin (1.7 ± 0.3 vs 0.9 ± 0.1 μg/mL for HFD1/2 and LFD1/2 groups, respectively) and leptin levels (14.9 ± 5 vs 3.9 ± 1 μg/mL for HFD1/2 and LFD1/2 groups, respectively) were also significantly (p < 0.05) increased in the HFD1/2 group, while no significant difference was observed in the fasting blood glucose concentration between the midpoint groups. Both groups presented similar levels of oxidative stress and inflammatory markers, except for the GSSG/TGSH ratio and IL-6 (pro-inflammatory) which were significantly (p < 0.05) higher in the HFD1/2 group (Supporting Information Table S1). Body Weight, Body Fat Content, and Intestinal Tissue Weight. The development of body weights of mice during both periods of the study was displayed in Figure 2A. The body weight gain during the second period of the experiment (weeks 10−17), i.e., the difference of weight between week 17 and week 10, was calculated and shown in Figure 2B. The body weight gain of the HFD control group was significantly higher than that of the LFD group (Figure 2B). The HFD control group also had twice the weight of subcutaneous and visceral adipose tissues as compared to the LFD group (Figure 2C,D). The change from the high-fat diet to low-fat diet for the second period (HFD + LFD or “lifestyle” group) resulted in a rapid weight loss within the first 2 weeks after the dietary change (Figure 2A) and in the reduction of the weight of the adipose tissues (Figure 2C,D), reaching levels similar to the low-fat-diet control group (LFD). The group receiving the high-fat diet enriched with the ultrafine ground wheat aleurone (A-G group) had the highest increase in body weight gain, which was significantly different (p < 0.05, ANOVA) from the body weight gain in the HFD control group (Figure 2B). Groups receiving high-fat diets enriched with native aleurone, enzymatically treated aleurone fractions, or commercial FA had body weight gain similar to that of the HFD control group (Figure 2B). In addition, there were no significant differences in the weights of the adipose tissues between the HFD control group and aleurone- or FAenriched diets (Figure 2C,D). Although the group receiving aleurone treated with xylanase and feruloyl esterase (AXYNFAE) had results statistically similar to those of HFD, a tendency toward reduced body weight gain (33% reduction, p = 0.07 t-test) and lower visceral adipose tissue amount (23% reduction, p = 0.004 t-test) was observed when comparing only these two groups (A-XYNFAE and HFD) by the t-test. Body weight gain and adipose tissue accumulation in the A-XYNFAE group was indeed found statistically similar to that of the LFD control (Figure 2B−D). All groups receiving high-fat diet had similar energy intake regardless of aleurone enrichment (Table 2). Only the low-fat-fed groups (LFD and lifestyle HFD + LFD group) had significantly lower energy intake ((kcal/mouse)/ day) as compared to HFD groups (Table 2). All diets enriched with wheat aleurone preparations produced intestinal tissue of similar weight of compared those from HFD, except A-XYNFAE which had significant (p < 0.05, ANOVA) higher weight of intestinal tissue than the HFD control (Table 2). Cecal and colon tissue weights were not significantly changed by enriched aleurone diets or free FA compared to the HFD control group.

37.2 ± 1.3ab 3.12 ± 0.06d 14.6 ± 0.2abc 0.74 ± 0.03c 0.057 ± 0.00b 0.15 ± 0.01a 9.4 ± 0.7a

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Blood Plasma Parameters (Glucose, Insulin, and Leptin Levels). The fasting blood glucose level was similar between all the groups (Table 2). The fasting insulin levels were doubled in the HFD group as compared to the LFD group (Figure 3A). The change from the high-fat diet to low-fat

Oxidative Stress and Inflammation. All of the data for oxidative and inflammatory markers are displayed in the Supporting Information (Table S2). High-fat diet feeding did not result in significant changes of the oxidative or inflammatory markers as compared to the LFD control group. Neither the aleurone-enriched diets nor C-FA-enriched diet had any beneficial impact on the levels of protein oxidation, the total antioxidant capacity, TBARS, TGSH, GSSG, GSSG/ TGSH, CRP, pro (IL-1β, IL-6), or anti-inflammatory cytokines (IL-10) as compared to HFD. The only oxidative marker affected by the diets was the LPO. The aleurone-enriched diet A-XYN (LPO = 15.9 ± 1.9 nmol/g) and the C-FA (LPO = 16.4 ± 0.8 nmol/g) diet reduced the LPO levels significantly (p < 0.05, ANOVA) by 25% and 22%, respectively, as compared to the HFD control diet (LPO = 21.1 ± 0.8 nmol/g). The LPO levels did not change in the other groups (LPO = 18−20 nmol/ g). Furthermore, no differences in the activity of the antioxidant enzymes catalase, GPx, and SOD were observed between the study groups.

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DISCUSSION In the present work, the structure of the wheat aleurone was disrupted (by physical and enzymatic methods), and the effects of this disintegration on obesity and associated metabolic disorders in DIO mice were studied in a curative design. A curative design means that aleurone-enriched diets were provided to mice previously induced to develop obesity by feeding for 9 weeks with a high-fat diet. The amount of aleurone (13%) added in the high-fat diet provided a diet with 5% dietary fiber to mice, which is a common fiber (usually cellulose) level used in mice studies. Effects of Native and Processed Aleurone on Obese Mice. Enrichment of the high-fat diet with 13% native wheat aleurone (group A-N) had no impact on the reversal of obesity in DIO mice. Other studies have also observed that high-fat diet supplemented with aleurone in corresponding amounts to those used in this study (10% for 3 weeks)14 or wheat bran (16.5% for 12 weeks)34 did not reduce the obesity of mice or rats in a preventive design. A preventive design means that no prefeeding period with high-fat diet was performed; i.e., the studied compound was added to the diet already in the beginning of the experiment. On the other hand, a recent study by Neyrinck et al.12 showed that a high-fat diet (60E%) supplemented with purified AX from wheat (10% (w/w)) for 4 weeks in a preventive design decreased adiposity, body weight gain, serum and hepatic cholesterol accumulation, and insulin resistance in mice and that these effects were related to changes in the gut microbiota. The difference of the results obtained by Neyrinck et al.12 as compared to the results found in our study could be attributed to the higher amount of purified AX (around 2.5-fold higher) and/or the preventive design of the study. If native aleurone had no impact on the reversal of obesity in DIO mice in our study, the ultrafine ground aleurone (group A-G) surprisingly increased (p < 0.05, Figure 2B) the body weight gain of mice as compared to the HFD control. The native and ground aleurones had a similar amount of insoluble AX and bound FA. Ultragrinding increased the aleurone particle surface area exposed to digestive enzymes, probably rendering the digestion more efficient. This could have led mice to increase their gain of weight when supplemented with ultraground aleurone instead of a native one or only a high-fat diet.

Figure 3. Plasma levels of (A) insulin and (B) leptin at the end of the experiment (week 17). The values are reported as means ± SEM. Values not significantly different (p > 0.05) are designated by pairs of letters.

diet (HFD + LFD lifestyle group) normalized the fasting insulin levels to the level observed in the LFD control group. Enrichment with aleurone preparations or commercial FA had no significant effect on insulin levels compared to the control HFD group (Figure 3A). However, A-XYNFAE had a tendency toward lowered fasting insulin levels (30% reduction, p = 0.07 ttest) compared to the HFD control group. A similar trend was observed for the C-FA group (35% reduction, p = 0.03 t-test) compared to the HFD control group. The level of plasma leptin was 5.8-fold higher in the HFD group than in the LFD group (Figure 3B). The change from the high-fat diet to low-fat diet (HFD + LFD lifestyle group) resulted in reduction of leptin concentrations to the same level as in the LFD group. No significant differences in leptin levels were found between the HFD and aleurone-enriched groups. The group A-XYNFAE was the only one that had a tendency toward a reduced leptin level (44% reduction, p = 0.02 t-test) as compared to the HFD control group (Figure 3b). The level of leptin in all groups was positively correlated with the amount of adipose tissue in mice (r = 0.98 and 0.93 for visceral and subcutaneous, respectively). 10106



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groups (p = 0.01 and p = 0.03, respectively, ANOVA) may be related to the high antioxidant capacity of these diets due to the high amount of bioaccessible FA, which was shown to scavenge free radicals from the lipid phase and quench the lipid peroxides.41 However, the fact that the A-XYNFAE diet did not reduce LPO levels despite its high antioxidant capacity remains unclear. Other studies have also shown that supplementation with free FA and feruloyl oligosaccharides from wheat bran decreases oxidative stress biomarkers in high-cholesterol, diabetic, and normal rats.42−44 Even though the HFD control group had higher levels of obesity, fasting plasma insulin and leptin compared to LFD throughout the experiment, HFD did not have any significant impact on the degree of oxidative stress or the inflammatory marker levels as compared to LFD. Similarly to our results, Hogan et al.45 also observed that 12 weeks of a high fat diet feeding was not enough to induce oxidative stress in C57BL/6J mice when compared to a normal diet. It is noteworthy that despite the high amount of fat (45 E%), mainly saturated lard, present in the high-fat diet used in our study, the diet also contained adequate amounts of vitamins and minerals which can help the body metabolism to cope with potential oxidative stress. Therefore, more robust models of feeding trials such as cafeteria diets might be useful in future studies.46 In conclusion, this study showed that enrichment of diet with native aleurone reduced neither obesity nor oxidative stress and inflammatory status of DIO mice, but high-fat diets enriched with processed aleurone could impact some parameters of mice metabolism. Disruption of the physical structure of aleurone by ultrafine grinding was not beneficial, as it slightly increased the body weight gain of mice. Disintegration of aleurone at the molecular level showed some trends to reduce body weight gain, visceral adiposity, leptin level, and fasting insulin level in DIO mice, probably related to their higher content in soluble fiber, bioaccessible FA, and other phytochemicals. Considering the cost of aleurone milling and enzymatic treatments, it seems that the use of native or processed aleurone to counteract the metabolic disorders caused by obesity is limited. The lack of significant improvements was probably due to the curative design of this study, which aimed to reverse mice obesity by aleurone-enriched diets. The trends toward improvements of obesity observed by enzymatic treated aleurone indicates that it might be of interest to study the nutritional potential of processed aleurone on healthy mice fed with a high-fat diet in a preventive design.

The disruption of aleurone by enzymatic treatment with the xylanase and feruloyl esterase (A-XYNFAE group) only showed a tendency (p = 0.07, t-test) toward reduced body weight gain as compared to the HFD group. A similar tendency toward lower visceral adipose tissue and secretion of leptin was observed when comparing only A-XYNFAE and HFD by t-test (p = 0.004 and p = 0.02 for visceral adipose tissue and leptin, repectively). A-XYNFAE diet had the highest proportion of soluble AX (75%) and conjugated and free forms of ferulic acid (85% of the total FA, respectively) in comparison to other aleurone fractions. Free and conjugated FA forms were reported to be bioavailable already in the upper part of the intestinal tract of humans and mice and beneficial against obesity in rodents.35,36 Son et al.37 observed that mice fed during 7 weeks with a free FA enriched high-fat diet in a preventive design reduced their body weight gain. In our work, however, mice fed the C-FA diet (100% free FA) did not have any significant reduction in the body weight gain or adiposity. This discrepancy between the two studies might be due to the 5-fold lower FA dose we administrated and to the curative design of our work. Since C-FA diet had no effect on the body weight gain of mice, the A-XYNFAE tendency could be more related to the high amount of soluble AX in this fraction. Soluble fiber can reduce the obesity by contributing to the viscosity of digesta in the small intestine delaying gastric emptying and decreasing the rate of lipid and carbohydrate absorption in the digestive tract.38,39 Soluble AX fibers were also demonstrated to impact on the microbial metabolism (i.e., the formation of SCFA, gases, and phenolic metabolites) using an in vitro gut model with faecal microbiota as an inoculum.20 However, the beneficial effects of the enzymatic solubilization of AX on mice obesity remained here as a minor trend, and it might be more pronounced adding the A-XYNFAE diet in a preventive way. Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In our study the 17 weeks high-fat diet feeding tended to increase fasting blood glucose as compared to the low-fat control group (p = 0.02, ttest), but neither aleurone- nor FA-enriched diets had any effect on the fasting blood glucose. However, AXYNFAE and C-FA groups had a tendency toward lower fasting plasma insulin level compared to HFD (p = 0.07 for AXYNFAE and p = 0.03 for CFA, t-test). This tendency to better insulin sensitivity might be related to the high amount of bioacessible FA in both groups rather than to their soluble AX fiber contents, as the C-FA diet contained only cellulose as fiber. Free FA has been previously shown to improve insulin sensitivity in diabetic rats,40 suggesting that the different effects observed might be due the dose, longer feeding period (19 weeks), and preventive design. Effects of Native and Processed Aleurone on Oxidative Stress and Inflammatory Status. There were no significant differences between the aleurone fractions, C-FA, and control groups for most of the markers for oxidative stress or inflammation. Similarly in healthy humans, the enrichment of the diet with aleurone (amount of aleurone corresponding to 1% of the diet, which provided around 15 g of dietary fiber from aleurone) during a 4 week period did not change the plasma antioxidant activity or markers of inflammation, CRP being the only one decreased after consuming aleurone.16 In our study, the only marker significantly affected by the diets was the lipid peroxidation byproduct lipidhydroperoxides (LPO). The significant decrease in the LPO levels in A-XYN and C-FA

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ASSOCIATED CONTENT

S Supporting Information *

Status of mice in the end of the first period (midpoint groups HFD1/2 and LFD1/2; Table S1) and oxidative and inflammatory markers of mice fed high-fat diet enriched with aleurone fractions (end of the second period; Table S2). This material is available free of charge via the Internet at http:// pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Tel.: +33 4 99 61 28 89. Fax: +33 4 99 61 30 76. Funding

The project was financed by the price Chercheur d’Avenir 2009 (Région Languedoc-Roussillon) awarded to V. M,. and it was 10107



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(11) Lu, Z. X.; Walker, K. Z.; Muir, J. G.; O’Dea, K. Arabinoxylan fibre improves metabolic control in people with Type II diabetes. Eur. J. Clin. Nutr. 2004, 58, 621−628. (12) Neyrinck, A. M.; Possemiers, S.; Druart, C.; Van de Wiele, T.; De Backer, F.; Cani, P. D.; Larondelle, Y.; Delzenne, N. M. Prebiotic effects of wheat arabinoxylan related to the increase in bifidobacteria, Roseburia and Bacteroides/Prevotella in diet-induced obese mice. PLoS One 2011, 6, 20944−20944. (13) Zhao, Z. H.; Moghadasian, M. H. Chemistry, natural sources, dietary intake and pharmacokinetic properties of ferulic acid: A review. Food Chem. 2008, 109, 691−702. (14) Neyrinck, A. M.; De Backer, F.; Cani, P. D.; Bindels, L. B.; Stroobants, A.; Portetelle, D.; Delzenne, N. M. Immunomodulatory properties of two wheat bran fractionsaleurone-enriched and crude fractionsin obese mice fed a high fat diet. Int. Immunopharmacol. 2008, 8, 1423−1432. (15) Sagara, M.; Mori, M.; Mori, H.; Tsuchikura, S.; Yamori, Y. Effect of dietary wheat aleurone on blood pressure and blood glucose and its mechanisms in obese spontaneously hypertensive rats: Preliminary report on comparison with a soy diet. Clin. Exp. Pharmacol. Physiol. 2007, 34, S37−S39. (16) Price, R. K.; Wallace, J. M. W.; Hamill, L. L.; Keaveney, E. M.; Strain, J. J.; Parker, M. J.; Welch, R. W. Evaluation of the effect of wheat aleurone-rich foods on markers of antioxidant status, inflammation and endothelial function in apparently healthy men and women. Br. J. Nutr. 2012, 108, 1644−1651. (17) Hemery, Y. M.; Anson, N. M.; Havenaar, R.; Haenen, G. R. M. M.; Noort, M. W. J.; Rouau, X. Dry-fractionation of wheat bran increases the bioaccessibility of phenolic acids in breads made from processed bran fractions. Food Res. Int. 2010, 43, 1429−1438. (18) Rosa, N. N.; Barron, C.; Gaiani, C.; Dufour, C.; Micard, V. Ultra-fine grinding increases the antioxidant capacity of wheat bran. J. Cereal Sci. 2013, 57, 84−90. (19) Rosa, N. N.; Dufour, C.; Lullien-Pellerin, V.; Micard, V. Exposure or release of ferulic acid from wheat aleurone: Impact on its antioxidant capacity. Food Chem. 2013, 141, 2355−2362. (20) Rosa, N. N.; Aura, A. M.; Saulnier, L.; Holopainen-Mantila, U.; Poutanen, K.; Micard, V. Effects of disintegration on in vitro fermentation and conversion patterns of wheat aleurone in a metabolical colon model. J. Agric. Food Chem. 2013, 61, 5805−5816. (21) Stewart, M. L.; Slavin, J. L. Particle size and fraction of wheat bran influence short-chain fatty acid production in vitro. Br. J. Nutr. 2009, 102, 1404−1407. (22) Zaupa, M.; Scazzina, F.; Dall’Asta, M.; Calani, L.; Del Rio, D.; Bianchi, M. A.; Melegari, C.; De Albertis, P.; Tribuzio, G.; Pellegrini, N.; Brighenti, F. In vitro bioaccessibility of phenolics and vitamins from durum wheat aleurone fractions. J. Agric. Food Chem. 2014, 62, 1543−1549. (23) Mateo Anson, N.; Aura, A.-M.; Selinheimo, E.; Mattila, I.; Poutanen, K.; van den Berg, R.; Havenaar, R.; Bast, A.; Haenen, G. R. M. M. Bioprocessing of wheat bran in whole wheat bread increases the bioavailability of phenolic acids in men and exerts antiinflammatory effects ex vivo. J. Nutr. 2011, 141, 137−43. (24) Mateo Anson, N.; Selinheimo, E.; Havenaar, R.; Aura, A.-M.; Mattila, I.; Lehtinen, P.; Bast, A.; Poutanen, K.; Haenen, G. R. M. M. Bioprocessing of wheat bran improves in vitro bioaccessibility and colonic metabolism of phenolic compounds. J. Agric. Food Chem. 2009, 57, 6148−6155. (25) Lappalainen, Z.; Lappalainen, J.; Oksala, N. K.; Laaksonen, D. E.; Khanna, Z. S.; Sen, C. K.; Atalay, M. Diabetes impairs exercise training-associated thioredoxin response and glutathione status in rat brain. J. Appl. Physiol. 2009, 106, 461−467. (26) Sunderman, F. W., Jr.; Marzouk, A.; Hopfer, S. M.; Zaharia, O.; Reid, M. C. Increased lipid peroxidation in tissues of nickel chloridetreated rats. Ann. Clin. Lab. Sci. 1985, 15, 229−236. (27) Kinnunen, S.; Oksala, N. K. J.; Hyyppä, S.; Sen, C. K.; Radak, Z.; Laaksonen, D. E.; Szabo, B.; Jakus, J.; Atalay, M. Alpha-Lipoic acid modulates thiol antioxidant defenses and attenuates exercise-induced

also supported by Agropolis Foundation, OCDE and AFFRST. P.h.D funding for N.N.R. was provided by the French National Education Ministry. J.P. is grateful to the The Finnish Graduate School on Applied Biosciences: Bioengineering, Food & Nutrition, Environment. J.P., K.H., and H.M. are grateful to the Nordforsk Nordic Centre of Excellence project “HELGA Whole grains and health”. Support from the Academy of Finland to K.P. is gratefully acknowledged. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank A. Putois (UMR IATE-Montpellier), B. Bonnafos (UMR Dynamique Musculaire et Métabolisme-Montpellier), and S. Martilla (UEF-Kuopio) for skilful technical assistance. W. von Reding (Bühler SA, Switzerland) is thanked for providing the native wheat aleurone. J. F. Sørensen (Danisco, Denmark) and C. Faulds (IFR, Norwich, U.K.) are thanked for kindly providing the enzymes Grindamyl Powerbake 950 and feruloyl esterase, respectively.

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ABBREVIATIONS A-N, native aleurone diet; A-G, ground aleurone diet; A-XYN, xylanase treated aleurone diet:; A-XYNFAE, xylanase and feruloyl esterase treated aleurone diet; AX, arabinoxylans; CFA, commercial ferulic acid diet; DIO, diet-induced obesity; FA, ferulic acid; HFD, high-fat diet; LFD, low-fat diet; TEAC, Trolox equivalent antioxidant capacity

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REFERENCES

(1) Eckel, R. H.; Grundy, S. M.; Zimmet, P. Z. The metabolic syndrome. Lancet 2005, 365, 1415−1428. (2) Vincent, H. K.; Taylor, A. G. Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int. J. Obes. 2006, 30, 400−418. (3) McKeown, N. M.; Yoshida, M.; Shea, M. K.; Jacques, P. F.; Lichtenstein, A. H.; Rogers, G.; Booth, S. L.; Saltzman, E. Whole-grain intake and cereal fiber are associated with lower abdominal adiposity in older adults. J. Nutr. 2009, 139, 1950−1955. (4) Bazzano, L. A.; Song, Y. Q.; Bubes, V.; Good, C. K.; Manson, E.; Liu, S. Dietary intake of whole and refined grain breakfast cereals and weight gain in men. Obes. Res. 2005, 13, 1952−1960. (5) Fardet, A. New hypotheses for the health-protective mechanisms of whole-grain cereals: What is beyond fibre? Nutr. Res. Rev. 2010, 23, 65−134. (6) Brouns, F.; Hemery, Y.; Price, R.; Anson, N. M. Wheat aleurone: Separation, composition, health aspects, and potential food use. Crit. Rev. Food Sci. Nutr. 2012, 52, 553−568. (7) Hemery, Y.; Rouau, X.; Lullien-Pellerin, V.; Barron, C.; Abecassis, J. Dry processes to develop wheat fractions and products with enhanced nutritional quality. J. Cereal Sci. 2007, 46, 327−347. (8) Saulnier, L.; Sado, P. E.; Branlard, G.; Charmet, G.; Guillon, F. Wheat arabinoxylans: Exploiting variation in amount and composition to develop enhanced varieties. J. Cereal Sci. 2007, 46, 261−281. (9) Barron, C.; Surget, A.; Rouau, X. Relative amounts of tissues in mature wheat (Triticum aestivum L.) grain and their carbohydrate and phenolic acid composition. J. Cereal Sci. 2007, 45, 88−96. (10) Garcia, A. L.; Otto, B.; Reich, S. C.; Weickert, M. O.; Steiniger, J.; Machowetz, A.; Rudovich, N. N.; Möhlig, M.; Katz, N.; Speth, M.; Meuser, F.; Doerfer, J.; Zunft, H.-F.; Pfeiffer, A. H. F.; Koebnick, C. Arabinoxylan consumption decreases postprandial serum glucose, serum insulin and plasma total ghrelin response in subjects with impaired glucose tolerance. Eur. J. Clin. Nutr. 2007, 61, 334−341. 10108



Article

oxidative stress in standardbred trotters. Free Radical Res. 2009, 43, 697−705. (28) Faure, P.; Lafond, J. Measurement of plasma sulfhydryl and carbonyl groups as a possible indicator of protein oxidation. In Analysis of free radicals in biological systems; Favier, A., Cadet, J., Kalyanaraman, B., Fontecave, M., Pierre, J., Eds.; Birkhauser Verlag: Basel, Switzerland, 1995; pp 237−248. (29) Oksala, N. K. J.; Paimela, H.; Alhava, E.; Atalay, M. Heat shock preconditioning induces protein carbonylation and alters antioxidant protection in superficially injured guinea pig gastric mucosa in vitro. Dig. Dis. Sci. 2007, 52, 1897−1905. (30) Kinnunen, S.; Hyyppa, S.; Lehmuskero, A.; Oksala, N.; Mäenpäa,̈ P.; Hänninen, O.; Atalay, M. Oxygen radical absorbance capacity (ORAC) and exercise-induced oxidative stress in trotters. Eur. J. Appl. Physiol. 2005, 95, 550−556. (31) Beers, R.; Sizer, I. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J. Biol. Chem. 1952, 195, 133−140. (32) Flohe, L.; Gunzler, W. A. Assays of glutathione peroxidase. Methods Enzymol. 1954, 105, 114−121. (33) Marklund, S. Spectrophotometric study of spontaneous disproportionation of superoxide anion radical and sensitive direct assay for superoxide dismutase. J. Biol. Chem. 1976, 251, 7504−7507. (34) Belobrajdic, D. P.; Lam, Y. Y.; Mano, M.; Wittert, G. A.; Bird, A. R. Cereal based diets modulate some markers of oxidative stress and inflammation in lean and obese Zucker rats. Nutr. Metab. 2011, 8, 27. (35) Andreasen, M. F.; Kroon, P. A.; Williamson, G. Esterase activity able to hydrolyze dietary antioxidant hydroxycinnamates is distributed along the intestine of mammals. J. Agric. Food Chem. 2001, 49, 5679− 5684. (36) Hsu, C.-L.; Yen, G.-C. Phenolic compounds: Evidence for inhibitory effects against obesity and their underlying molecular signaling mechanisms. Mol. Nutr. Food Res. 2008, 52, 53−61. (37) Son, M. J.; Rico, C. W.; Nam, S. H.; Kang, M. Y. Influence of oryzanol and ferulic acid on the lipid metabolism and antioxidative status in high fat-fed mice. J. Clin. Biochem. Nutr. 2010, 46, 150−156. (38) Brennan, C. S. Dietary fibre, glycaemic response, and diabetes. Mol. Nutr. Food Res. 2005, 49, 560−570. (39) Davidson, M. H.; McDonald, A. Fiber: Forms and functions. Nutr. Res. (N. Y., NY, U. S.) 1988, 18, 617−624. (40) Choi, R.; Kim, B. H.; Naowaboot, J.; Lee, M. Y.; Hyun, M. R.; Cho, E. J.; Lee, E. S.; Lee, E. Y.; Yang, Y. C.; Chung, C. H. Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes. Exp. Mol. Med. 2011, 43, 676−683. (41) Srinivasan, M.; Rukkumani, R.; Sudheer, A. R.; Menon, V. P. Ferulic acid, a natural protector against carbon tetrachloride-induced toxicity. Fundam. Clin. Pharmacol. 2005, 19, 491−496. (42) Ou, S. Y.; Jackson, G. M.; Jiao, X.; Chen, J.; Wu, J.-Z.; Huang, X.-S. Protection against oxidative stress in diabetic rats by wheat bran feruloyl oligosaccharides. J. Agric. Food Chem. 2007, 55, 3191−3195. (43) Wang, J.; Sun, B.; Cao, Y. Wheat bran feruloyl oligosaccharides enhance the antioxidant activity of rat plasma. Food Chem. 2010, 123, 472−476. (44) Yeh, Y. H.; Lee, Y. T.; Hsieh, H. S.; Hwang, D. F. Dietary caffeic acid, ferulic acid and coumaric acid supplements on cholesterol metabolism and antioxidant activity in rats. J. Food Drug Anal. 2009, 17, 123−132. (45) Hogan, S.; Canning, C.; Sun, S.; Sun, X.; Zhou, K. Effects of grape pomace antioxidant extract on oxidative stress and inflammation in diet induced obese mice. J. Agric. Food Chem. 2010, 58, 11250− 11256. (46) Sampey, B. P.; Vanhoose, A. M.; Winfield, H. M.; Freemerman, A. J.; Muehlbauer, M. J.; Fueger, P. T.; Newgard, C. B.; Makowski, L. Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: Comparison to high-fat diet. Obesity 2011, 19, 1109−1117.

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Impact of Wheat Aleurone Structure on Metabolic Disorders Caused

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