Pineapple Vinegar Regulates Obesity-Related Genes and Alters the Gut Microbiota in High-Fat Diet (HFD) C57BL/6 Obese Mice

Mohamad, Nurul Elyani; Yeap, Swee Keong; Ky, Huynh; Liew, Nancy Woan Charn; Beh, Boon Kee; Boo, Sook Yee; Ho, Wan Yong; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

doi:https://doi.org/10.1155/2020/1257962

Evidence-Based Complementary and Alternative Medicine

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Abstract Introduction Materials and Methods Results Discussion Conclusions Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2020 | Article ID 1257962 | https://doi.org/10.1155/2020/1257962

Pineapple Vinegar Regulates Obesity-Related Genes and Alters the Gut Microbiota in High-Fat Diet (HFD) C57BL/6 Obese Mice

Nurul Elyani Mohamad,¹Swee Keong Yeap,²Huynh Ky,³Nancy Woan Charn Liew,⁴Boon Kee Beh,¹Sook Yee Boo,⁵Wan Yong Ho,⁶Shaiful Adzni Sharifuddin,⁷Kamariah Long,⁷and Noorjahan Banu Alitheen¹

Academic Editor: Cristina Nogueira

Received05 May 2020

Revised12 Aug 2020

Accepted05 Sept 2020

Published23 Sept 2020

Abstract

Obesity is a pandemic metabolic syndrome with increasing incidences every year. Among the significant factors that lead to obesity, overconsumption of high-fat food in daily intake is always the main contributor. Functional foods have shown a positive effect on disease prevention and provide health benefits, including counteracting obesity problem. Vinegar is one of the fermented functional beverages that have been consumed for many years, and different types of vinegar showed different bioactivities and efficacies. In this study, we investigated the potential effects of pineapple vinegar as an antiobesity agent on a high-fat diet- (HFD-) induced C57BL/6 obese mice. C57BL/6 mice were treated with pineapple vinegar (1 mL/kg BW and 0.08 mL/kg BW) for 12 weeks after 24 weeks of HFD incubation. Serum biochemistry profiles, antioxidant assays, qPCR, proteome profiler, and 16S metagenomic were done posttreatment. Our data showed that a high concentration of pineapple vinegar (1 mL/kg BW) treatment significantly () reduced the bodyweight (∼20%), restored lipid profiles, increased the antioxidant activities, and reduced the oxidative stress. Besides, significant () regulation of several adipokines and inflammatory-related genes was recorded. Through the regulation of gut microbiota, we found a higher abundance of Akkermansia muciniphila, a microbiota reported to be associated with obesity in the high concentration of pineapple vinegar treatment. Collectively, these data established the mechanism of pineapple vinegar as antiobesity in mice and revealed the potential of pineapple vinegar as a functional food for obesity.

1. Introduction

Excessive consumption of food and an imbalanced diet has led to severe obesity issues in many people. As the food industry develops, the relative ease in procuring high-fat foods with low nutritional value has contributed to the increasing obesity cases [1, 2]. Furthermore, obesity is not an isolated case, but instead, it has a far-reaching impact on other diseases such as cancer and cardiovascular disease [3, 4]. Obesity is caused by the increase in adipocyte numbers and volume in the body [5, 6]. Adipocyte not only plays essential roles in fat storage but also involves in metabolic function and endocrine system of the body [7]. The alteration of adipose tissue leads to an increase of proinflammatory molecules and adipokines [8]. The relationship between obesity and inflammation has been studied for many years, and it was found that inflammation is one of the significant indicators linking to obesity [9, 10].

Functional food contains phytochemicals and bioactive compounds, which help to improve body function [11] and, consequently, alter the gut microbiota [12]. The use of functional food in treating obesity has long been investigated [13]. Fruits and vegetables which contain high antioxidants and minerals are examples of natural resources of functional foods [14–16]. Antioxidant has been proven to be one of the anti-inflammatory agents and plays a vital role in reducing weight through several mechanisms [17–19]. Studies showed that the consumption of fruit markedly decreased the risk of cardiovascular disease, which might be contributed by the presence of a high level of antioxidants and nutrients in the fruit [20–22]. The benefits conferred on the body by the consumption of fruits are at its peak when it is consumed fresh. However, fruits rot quickly in the tropical climate, especially when the supply exceeds the demand, and with improper handling, it causes an increase in fruit wastage worldwide, including in Malaysia [23–26]. To overcome this problem, fruits can be kept in several forms, including fermenting them into vinegar [25, 27].

Vinegar is one of the functional drinks that has been consumed not only for health maintenance but also to assist in the weight loss process [28, 29]. As vinegar can be made using various carbohydrate sources such as fruits, which is rich in antioxidants such as quercetin, it may assist in the weight loss process [30, 31]. A recent study on tomato vinegar has found that this vinegar exhibited in vitro and in vivo antiobesity effects [32, 33]. Tomato is rich with antioxidants and well known for its anti-inflammatory effect, which may be the factor that contributed to the antiobesity effect of tomato vinegar [34, 35]. In addition, coconut water vinegar and nipa vinegar were also reported with anti-inflammatory and antiobesity effects [36, 37].

Pineapple is one of the local fruits and is in abundance in Malaysia. It contains high vitamin C content and other antioxidants, which helps to enhance the immunity and protect the body from various diseases [38, 39]. It has been researched thoroughly and is reported to possess anti-inflammatory activity [40]. This is consistent with the data from our previous study, where antioxidant and anti-inflammatory activities have been shown by pineapple vinegar when tested in vivo [41]. As the bioactivities of vinegar were found to be varied due to the starting materials to prepare the vinegar [36], this study was conducted to investigate the antiobesity potential of pineapple vinegar using C57BL/6 mice fed with high-fat diets. Here, we performed several molecular assays and ran 16S metagenomic analysis to further explore the mechanism effect of pineapple vinegar in assisting the weight reduction. As far as we know, this is the first report on the antiobesity potential of pineapple vinegar tested in vivo.

2. Materials and Methods

2.1. Sample Preparation

Pineapple vinegar containing 6–8% of acetic acid was produced from pineapple fruits by 7–10 days of anaerobic fermentation with S. cerevisiae 7013 INRA (28–30°C) following four weeks of aerobic fermentation with Acetobacter aceti vat Europeans (28–30°C) [41].

2.2. Animals

Seven-week-old male C57BL/6 mice (n = 24) were obtained from Monash University Malaysia Campus, Malaysia. All mice were acclimatized for seven days and were given standard pellet diet and distilled water ad libitum. The mice were placed in plastic cages at room temperature (22 ± 1°C) with 12 h of dark/light cycle and relative humidity approximately 60%. This study was done according to the guidelines and was approved by the Institution Animal Care and Use Committee (IACUC), Universiti Putra Malaysia (UPM/IACUC/AUP-R097/2014).

2.3. Experimental Design

The study was done according to previous studies [36, 37]. The mice were divided into three groups, with eight mice for each group as follows: UT: induced mice were given HFD + distilled water (control) PL: induced mice were given HFD + 0.08 mL/kg BW pineapple vinegar PH: induced mice were given HFD + 1 mL/kg BW pineapple vinegar

A high-fat diet (HFD, D12451, 45% kcal fat, Research Diet, USA) was used to induce obesity for 24 weeks in all mice. In brief, low-dose (PL, 0.08 ml/kg bodyweight (BW)) and high-dose (PH, 2 ml/kg BW) groups were given pineapple vinegar daily via oral gavage, starting from week 24 until week 33. Untreated obese control mice (UT) were given distilled water only. The pineapple vinegar dose was selected based on the previous in vivo study of the antioxidant effect of pineapple vinegar [41]. Bodyweight was measured once a week. At the end of the treatment, mice were sacrificed using the cervical dislocation method. Blood, liver, and white adipose tissue (gonadal fat pad) were collected from the mice before further analysis.

2.4. Biochemistry Profile

Blood was collected from all mice, and serum was separated using the microtainers (BD, USA). Sera were diluted 10x and tested for cholesterol, triglycerol, LDL, and HDL using a biochemical analyzer (Hitachi 902 Automatic Analyzer) and adapted reagents from Roche (Germany).

2.5. Determination of Antioxidant Activities in Liver Homogenate

The following antioxidant activities of pineapple vinegar in liver homogenate were done according to the methods described in our previous study [41].

2.5.1. FRAP Assay

The master solution consisted of acetate buffer, TPTZ, and FeCl₃⋅6H₂O solution at a ratio of 10 : 1 : 1 was prepared, wrapped in aluminium foil, and warmed to 37°C. Then, in a 96-well plate, 80 μL of liver homogenate and 150 μL of master solution were mixed and incubated for 10 minutes. The absorbance was read at 593 nm using an ELISA Plate Reader (Bio-Tek Instruments, USA). The activity was calculated from a standard FeSO₄ calibration curve.

2.5.2. SOD Assay

A serial dilution of liver homogenate (100 μL/well) was prepared in a 96-well plate. 200 μL of a master solution consisted of 0.1 mol/L phosphate buffer, 0.15 mg/mL sodium cyanide in 0.1 mol/L ethylene diamine tetraacetic acid (EDTA), and 1.5 mmol/L nitroblue tetrazolium, and 0.12 mmol/L riboflavin was then added to the plate before it was measured at 560 nm using an ELISA Plate Reader (Bio-Tek Instruments, USA).

2.5.3. MDA Assay

200 μL of liver homogenate was properly mixed with 800 μL of PBS, 25 μL of 8.8 mg/mL butylhydroxytoluene, and 500 μL of 50% trichloroacetic acid. The mixture was incubated for 2 hours on ice and centrifuged (MX-160 Tomy, Japan) at 2000 rpm for 15 min. Then, 1 mL of the supernatant was collected and transferred into a new tube to be added with 75 μL of 0.1 M EDTA and 250 μL of 0.05 M 2-thiobarbituric acid. After that, the mixture was boiled for 15 min, and the absorbance was measured at 532 nm and 600 nm using an ELISA Plate Reader (Bio-Tek Instruments, USA).

2.5.4. NO Assay

The assay was done following the manufacturer’s protocols for Griess reagent assay (Invitrogen, USA). In brief, 150 μL of liver homogenate was mixed with 20 μL of Griess reagent and 130 μL of distilled water in a 96-well plate. The mixture was incubated for 30 minutes and was measured at 540 nm using an ELISA Plate Reader (Bio-Tek Instruments, USA).

2.6. Gene Expression Analysis Using qRT-PCR

The mRNA expression of liver tissue was determined using real-time PCR following the methods described in the previous study [41]. In brief, the mRNA from the gonadal fat pad was extracted using the RNeasy Mini Kit (Qiagen, Germany). 1 μg of the total RNA was then reverse-transcribed to the first-strand cDNA using iScript™ Reverse Transcription Supermix for RT-qPCR (Bio-Rad, USA) according to the manufacturer’s protocols. Quantitative real-time PCR was performed with iTaq™ Universal SYBR® Green Supermix (Bio-Rad, USA). The quantities of the target genes and the housekeeping genes were calculated according to a standard curve, and the expressions were measured using iQ5 Software (Bio-Rad, USA). The expression levels in all samples were compared with those in the untreated group, and the levels of different mRNAs in the untreated group were designated as 1. All results were expressed as fold changes and measured in triplicate. Nontemplate controls were used to confirm specificity. The primer sequences used in the study are given in Table 1.

2.7. Proteome Profiler Assay (Adipokine)

The effect of pineapple vinegar on secreted cytokine from adipose tissue was analyzed using an adipokine proteome profiler kit (R&D System, USA). In brief, the membranes were blocked using blocking buffer at room temperature for 1 hour. Concurrently, the protein samples were incubated with the detection antibody at room temperature for 1 hour. Next, the protein samples, coupled with the detection antibody, were added to the membrane and incubated at 4°C overnight. The next day, the membranes were washed three times using a washing buffer and incubated with streptavidin-HRP for 30 minutes. Lastly, the membranes were rewashed three times before the substrate was added to develop chemiluminescence conditions. The membrane was then viewed using ChemiDoc XRS (Bio-Rad).

2.8. Metagenomic Study

Only untreated and high-concentration treatment groups were selected to undergo the metagenomic analysis. Faeces from week 20 (end treatment) were collected and kept at −80°C until further use. On a respected day, the faeces from each group were mashed using liquid nitrogen in an overnight baked pestle. The faeces were weighed, and the DNA was extracted using the QIAamp DNA stool mini kit (QIAGEN, Germany) according to the manufacturer’s protocol. The DNA was purified using Agencourt® AMPure® XP beads (Beckman Coulter, USA), and the concentration was measured using a Qubit fluorometer (Life Technologies, USA).

Amplification of 16S amplicon of V3 and V4 regions was done in the first PCR (forward primer:5′-CGTCGGCAGCGTCAGATGTGTATAAGAGACAGCCTACGGGNGGCWGC AG-3′; reverse primer:5′-GTCTCGTGGGCTCGGAGATGTGTATAAGAGACAGGACTACHVGGGTATCTAATCC-3′). In brief, 25 μl of DNA samples with a concentration of 12.5 ng of DNA, 12.5 μl of 2x KAPA Hifi Hot Start Ready Mix (Kapa Biosystems), and 1 μM of 16S amplicon PCR forward and reverse primer were mixed. The PCR was set to 95°C for 3 min, followed by 35 cycles for 30 s at 95°C, 30 s at 55°C, and 30 s at 72°C. The quality check for the first PCR product was done by purifying the product using Agencourt® AMPure® XP beads (Beckman Coulter, USA) before running them with the agarose gel to confirm the correct size. The second PCR will be commenced once all samples pass the quality check. The second PCR amplification was done by adding the product from the first PCR with the unique barcode using the Nextera XT index kit (Illumina, USA). In the second PCR amplification, 5 μl from the first PCR products, 25 μl of 2x KAPA Hifi Hot Start Ready Mix, and Nextera XT index Primers 1 and 2 were mixed. PCR was set to 95°C for 3 min, followed by eight cycles of 30 s at 95°C, 30 s at 55°C, and 30 s at 72°C and finally 5 min at 72°C. The quality check for the second PCR product was done using Agencourt® AMPure® XP beads and Agilent Bioanalyzer 2100 (Agilent Technologies, USA). Based on the bioanalyzer result, the concentration of the products was normalized to 4 nM and pooled together. Pooled samples were then prepared using the standard library protocols to a final concentration of 9 pM and ran on the MiSeq Sequencer (2 × 300 bp paired-end reads) (Illumina) using 600 cycles MiSeq V3 reagents (Illumina). The 16S metagenomics analysis was performed using Megan (MEtaGenome ANalyzer) based on BLASTX comparison against the NCBI database.

2.9. Statistical Analysis

All quantitative measurements were conveyed as mean ± standard deviation (SD). The analysis was performed using a one-way analysis of variance (ANOVA), and the group means were compared by the Duncan test. values <0.05 were considered as statistically significant.

3. Results

3.1. Pineapple Vinegar Reduces Bodyweight

Figure 1 shows that the consumption of a high-fat diet for 24 weeks led to an increase in the bodyweight of mice in all groups. As the treatment began, we can see that the weight of the mice in the untreated group continues to increase, while weight loss reduction was noticed in both pineapple vinegar treatment groups. The posttreatment assays revealed the significant () reduction in the percentage of gonadal adipose tissue over the bodyweight was recorded in the mice of high-concentration pineapple vinegar group as compared to the untreated group (Table 2).

3.2. Pineapple Vinegar Restores Lipid Serum Marker Enzyme

The effects of a high-fat diet and pineapple vinegar treatment in serum biomarkers are shown in Table 3. The serum level of cholesterol and triglyceride was the highest in the untreated group (G1), while the levels reduced significantly () in the pineapple vinegar treatment groups. Besides, significant () improvements were noted in the level of HDL/LDL ratio in the pineapple treatment groups compared to the untreated group.

3.3. Pineapple Vinegar Increases Antioxidant Activities

The antioxidant activities in this study were determined using several assays. A significant () increment in the antioxidant activity can be seen from the increase in FRAP and SOD levels and decreased NO and MDA levels. From Figure 2, a significant () increment of FRAP level was exhibited by pineapple vinegar treatments. On the contrary, pineapple vinegar treatment exhibited a significant () reduction of MDA and NO levels with high-concentration pineapple vinegar gave the most significant () results as compared to other treatment groups. However, no significant () effect was observed in the SOD enzyme activity across the tested groups.

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3.4. Pineapple Vinegar Regulates Obesity and Inflammatory-Related Genes

qRT-PCR was used to analyze the expression profiles of glucose transporter protein 4 (GLUT4), lipoprotein lipase (LPL), adiponectin (AD), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), inducible nitric oxide synthase (iNOS), and sterol regulatory element-binding protein (SREBP) genes in the gonadal fat pad of control and vinegar-treated mice. Figure 3 shows the mRNAs for the genes encoding GLUT4, LPL, AD, NF-κβ, iNOS, and SREBP. The highest upregulation of GLUT4 (∼7 folds), LPL (∼5 folds), and AD (∼2 folds) was associated with the highest downregulation of NF-κβ (∼2 folds), INOS (∼7 folds), and SREBP (∼4 folds) genes observed in the gonadal fat pad of mice treated with a high concentration of pineapple vinegar.

3.5. Pineapple Vinegar Regulates Adipokine Expression

The quantitative changes in the adipokine expression were analyzed with adipokine proteome profiler, and the downregulation of all adipokines was observed in the gonadal fat pad of mice treated with high concentration pineapple vinegar (Figure 4). The highest downregulation of adipokine expression was exhibited by RBP protein (∼15 folds) followed by resistin (∼13 folds), ANGPT-L3 (∼12 folds), IGFBP-3 (∼11 folds), ICAM-1 (∼11 folds), C-reactive protein (∼8 folds), and DPPIV (∼7 folds).

3.6. Pineapple Vinegar Alters Gut Microbiota

To evaluate the effect of pineapple vinegar on the alteration of gut microbiota population, NGS 16S rRNA metagenomic sequencing analysis was carried out. Figure 5 shows the quality control (QC) results of the metagenomic analysis, while Figure 6 exhibited the shift in the top 5 microbial compositions in all treatment groups. As depicted in the figure, the relative compositions of Akkermansia muciniphila and Lactobacillus hayakitensis increased by ∼16 folds and ∼4 folds, respectively, in the pineapple vinegar group compared to the untreated group. The differences in the microbial communities can be seen in Alkaliphilus crotonatoxidans, Bacteroides sartorii, and Sarcina maxima species. From the data, only the pineapple treatment group shows the presence of Alkaliphilus crotonatoxidans (∼4 folds), while no Bacteroides sartorii and Sarcina maxima species were detected in the pineapple vinegar treatment.

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4. Discussion

The obesity epidemic has become a serious health problem [3], and one of the factors that lead to this problem is the uncontrolled intake of dietary fat and sugar in daily life [42, 43]. Obesity is a systemic inflammatory response [44], and high levels of inflammation were found in many obese subjects [45, 46]. In the past years, studies offer the promise that several types of vinegar may help in reducing blood lipid, cholesterol, and fat accumulation and also improved the metabolic syndrome [32, 33, 36, 37, 46–48]. The study reported that the consumption of high-fat diet and obesity problems increased the cholesterol and triglyceride levels in the serum samples [49–51]. This is consistent with our data, where high levels of serum cholesterol and triglyceride were noticed in the untreated group.

Other than the elevation in the serum lipid profile and bodyweight, the consumption of a high-fat diet was also affiliated with an increase in oxidative stress [49–51]. MDA and NO are the by-products produced during oxidative stress [52]. Previous studies have proposed the effect of antioxidants in suppressing inflammation in the body [53, 54]. The antioxidant activities possessed by the pineapple vinegar may be one of the plausible factors contributing to the restoration of lipid serum and the regulation of all the genes and proteins in this study. Antioxidant plays a vital role in scavenging the free radicals formed from oxidative stress and restoring the level of cholesterol and triglyceride in the serum [55, 56]. From the overall results, the pineapple vinegar treatment significantly () reduced the bodyweight and the ratio of the fat pad over bodyweight, improved the levels of serum cholesterol, triglyceride, and the HDL/LDL ratio, enhanced the FRAP activity, and reduced the level of MDA and NO as compared to the untreated group.

In the qRT-PCR quantification, our data revealed that the expressions of GLUT4, LPL, and AD were upregulated, while SREBP was downregulated in the gonadal fat pad of pineapple vinegar-treated mice. To note, most of the obese subjects have a higher insulin level [57]. GLUT4 plays an important role in transporting glucose when the insulin level is detected to be low in the body [58]. As the level of GLUT4 increased in the pineapple vinegar treatment group, it suggests that the treatment with pineapple vinegar may involve in the reduction of insulin level in the body. In addition, LPL is the gene involved in the hydrolysis of triglyceride [59]. In conjunction with the upregulation of LPL by the pineapple vinegar, the level of serum triglyceride was found to be lower as compared to the untreated group. Adiponectin, on the contrary, is responsible for regulating glucose and fatty acid oxidation in the body [60]. The study found that an increase in adiponectin levels in the body contributed to the weight loss process [61], and this is consistent with our data observed in the pineapple vinegar-treated mice. In contrast, SREBP involved in the lipogenesis and the synthesis of cholesterol, fatty acid [62], and triglyceride [63], and in this study, significant () downregulation of SREBP was exhibited by the pineapple vinegar-treated mice.

Conversely, the positive correlations between the regulation of these genes with several adipokine proteins (IGFBP-3, ANGPT-L3, DPPIV, RBP 4, ICAM-1, and C-reactive protein) in the pineapple vinegar-treated mice are documented in Figure 7. The downregulation of IGFBP-3 was correlated with the inhibition of adipocyte proliferation through its capability to bind to IGF-1 and IGF-2 proteins. These IGF-1 and -2 proteins will subsequently suppress the IGF-1 receptor [64] and activate the insulin receptor [65]. The activation of the insulin receptor will then lead to an increase in GLUT4 expression [66]. These are consistent with our results shown in Figures 3 and 4. Besides IGFBP-3, angiopoietin-like 3 (ANGPT-L3) is another adipokine that is highly expressed in the liver and involves in the endothelial cell adhesion [67, 68]. The expression of ANGPT-L3 downregulated LPL and increased the level of plasma triglyceride [69–71]. Obesity was said to be associated with insulin resistance, and one of the factors that influence the insulin secretion is the blood glucose level and the expression of dipeptidyl-peptidase 4 (DPPIV) protein, which involves in the glucose metabolism [72, 73]. The presence of DPPIV inactivated incretin and glucagon-like peptide-1 (GLP-1) that is responsible for lowering the blood glucose, thus subsequently causing the elevation in blood glucose in the body [74, 75]. The downregulation of DPPIV in our data confirms the positive effect of pineapple vinegar in reducing obesity. Moreover, the regulation of retinol-binding protein 4 (RBP4) was also observed in the pineapple vinegar treatment group. RBP4 is involved in the insulin resistance process, where the upregulation of RBP4 was highly associated with obesity and diabetes type 2 problems [76]. The downregulation of RBP4 by pineapple vinegar also may be one of the factors contributing to the upregulation of GLUT4 expression in the qPCR result.

Obesity has been reported to be associated with acute inflammation, as the development of obesity promoted inflammation in the fat cells and adipose tissues [77, 78]. During the development of obesity, a high number of adipocytes were accumulated in the body, which promotes the onset of inflammation and thus increased the inflammatory-related genes, NF-kB, and iNOS [79, 80]. This obesity-induced inflammation will elevate the level of C-reactive protein, ICAM, and resistin, which subsequently increases the level of cholesterol in the blood [81–84]. In this study, a significant () downregulation of these inflammation-related genes (NF-κβ and iNOS) and inflammation-related adipokine proteins (C-reactive protein, ICAM, and resistin) were recorded in the pineapple vinegar treatment groups, which was in line with the decreased level of NO, MDA, and serum cholesterol level.

Previous studies have described a strong correlation between obesity and the profile of gut microbiota [85, 86]. In this study, the faeces microbiota profile within groups was compared using NGS 16S metagenomics study [87]. Based on the result, the population of Akkermansia muciniphila and Lactobacillus hayakitensis was 4 and 1.6 times higher in the pineapple vinegar treatment group as compared to the untreated mice, respectively. A. muciniphila was found abundant in the treated obese mice [88], and polyphenol was recently reported as one of the factors contributing to the growth of A. muciniphila [89]. The abundance of A. muciniphila in the pineapple vinegar-treated mice possibly contributed by the rich polyphenolic contents in the pineapple vinegar (gallic, caffeic, benzoic, sinapic, vanillic, β-hydroxybenzoic, protocatechuic, and syringic acids) [41]. In addition, the increased Lactobacillus hayakitensis in the pineapple vinegar treatment group showed a positive effect on obesity treatment. Lactobacillus is a group of bacterium that maintains good gut health, and the association of lactobacillus bacteria and obesity has been long discovered [90].

Interestingly, we found that Alkaliphilus crotonatoxidans was present in the pineapple vinegar group but absent in the untreated group. However, the role of A. crotonatoxidans in gut health was still not well documented. Our data also showed that Bacteroides satori and Sarcina maxima were only present in the untreated group. Previous studies have found that the presence of Bacteroides family in the gut of children led to a higher risk of developing obesity in adulthood [91, 92]. On the contrary, the Sarcina family has been reported to contribute to the incidence of gastrointestinal symptoms such as bloating and stomach ulcers, which are commonly associated with obesity [93]. The absence of Sarcina and Bacteroides species in the pineapple treatment group showed the positive effect of pineapple vinegar treatment towards weight reduction through a healthy gut microbiota population. Overall, the metagenomic profile may represent viable interventions in obesity prevention as these factors strongly related to obesity and other metabolic diseases.

Comparing the effect of pineapple vinegar with coconut water vinegar [36], nipa vinegar, and synthetic vinegar [37], all vinegar was observed with significant () body fat and bodyweight reduction. Besides, all treatments were also observed with reduced obesity-induced inflammation. Although all the fruits vinegar was reported with better effect than synthetic vinegar, different fruits vinegar still showed slight diverse in their bioactivities. More specifically, coconut water vinegar was reported to be the best effect to reduce bodyweight and fat pad/bodyweight ratio. On the contrary, pineapple vinegar was observed with the best effect to increase the HDL/LDL ratio and reduce related inflammation markers, including NO, inflammation-related genes, and adipokines. The superior anti-inflammatory effect may be contributed by the metabolites including gallic, caffeic, benzoic, sinapic, vanillic, β-hydroxybenzoic, protocatechuic, and syringic acids in the pineapple fruit [41, 94].

5. Conclusions

The antiobesity effects and the possible mechanism of pineapple vinegar were investigated in this study, and a summary of the overall mechanism is shown in Figure 7. Overall, pineapple vinegar regulated the expressions of several obesity-related genes and altered the gut microbiota to control inflammation and enhance the antioxidant level of mice with high-fat diet-induced obesity. Thus, pineapple vinegar can be used as a potential alternative functional food for obesity treatment.

Data Availability

The data used to support the findings of this study are included in the article.

Conflicts of Interest

The authors declare that there are no conflicts of interest.

Acknowledgments

The authors would also like to thank Professor Dr. Tan Soon Guan and Muhammad Firdaus Romli for proofreading the manuscript. This research was funded by the grant from Pembangunan RMK10 (project no. P2100300125), MARDI.

References

J. C. Seidell, “Prevention of obesity: the role of the food industry,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 9, no. 1, pp. 45–50, 1999.
View at: Google Scholar
S. D. Sugarman and N. Sandman, “Fighting childhood obesity through performance-based regulation of the food industry,” Duke Law Journal, vol. 56, no. 6, pp. 1403–1490, 2007.
View at: Google Scholar
W. H. Dietz, “Health consequences of obesity in youth: childhood predictors of adult disease,” American Academy of Pediatrics, vol. 101, no. 3, pp. 518–525, 1998.
View at: Google Scholar
G. Marchesini, S. Moscatiello, S. Di Domizio, and G. Forlani, “Obesity-associated liver disease,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 11, pp. s74–s80, 2008.
View at: Publisher Site | Google Scholar
P. Björntorp and L. Sjöström, “Number and size of adipose tissue fat cells in relation to metabolism in human obesity,” Metabolism, vol. 20, no. 7, pp. 703–713, 1971.
View at: Publisher Site | Google Scholar
M. Garaulet, J. J. Hernandez-Morante, J. Lujan, F. J. Tebar, and S. Zamora, “Relationship between fat cell size and number and fatty acid composition in adipose tissue from different fat depots in overweight/obese humans,” International Journal of Obesity, vol. 30, no. 6, pp. 899–905, 2006.
View at: Publisher Site | Google Scholar
A. S. Greenberg and M. S. Obin, “Obesity and the role of adipose tissue in inflammation and metabolism,” The American Journal of Clinical Nutrition, vol. 83, no. 2, pp. 461S–465S, 2006.
View at: Publisher Site | Google Scholar
S. P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R. L. Leibel, and A. W. Ferrante, “Obesity is associated with macrophage accumulation in adipose tissue,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1796–1808, 2003.
View at: Publisher Site | Google Scholar
R. J. Genco, S. G. Grossi, A. Ho, F. Nishimura, and Y. Murayama, “A proposed model linking inflammation to obesity, diabetes, and periodontal infections,” Journal of Periodontology, vol. 76, no. 11-s, pp. 2075–2084, 2005.
View at: Publisher Site | Google Scholar
P. Trayhurn and I. S. Wood, “Signalling role of adipose tissue: adipokines and inflammation in obesity,” Biochemical Society Transactions, vol. 33, no. 5, pp. 1078–1081, 2005.
View at: Publisher Site | Google Scholar
B. D. Oomah, “Flaxseed as a functional food source,” Journal of the Science of Food and Agriculture, vol. 81, no. 9, pp. 889–894, 2001.
View at: Publisher Site | Google Scholar
C. J. Ziemer and G. R. Gibson, “An overview of probiotics, prebiotics and synbiotics in the functional food concept: perspectives and future strategies,” International Dairy Journal, vol. 8, no. 5-6, pp. 473–479, 1998.
View at: Publisher Site | Google Scholar
S. Hirai, N. Takahashi, T. Goto et al., “Functional food targeting the regulation of obesity-induced inflammatory responses and pathologies,” Mediators of Inflammation, vol. 2010, Article ID 367838, 8 pages, 2010.
View at: Publisher Site | Google Scholar
F. Al-juhaimi, K. Ghafoor, M. M. Özcan et al., “Effect of various food processing and handling methods on preservation of natural antioxidants in fruits and vegetables,” Journal of Food Science and Technology, vol. 55, no. 10, pp. 3872–3880, 2018.
View at: Publisher Site | Google Scholar
H. Palafox-Carlos, J. F. Ayala-Zavala, and G. A. González-Aguilar, “The role of dietary fiber in the bioaccessibility and bioavailability of fruit and vegetable Antioxidants,” Journal of Food Science, vol. 76, no. 1, pp. R6–R15, 2011.
View at: Publisher Site | Google Scholar
A. E. Ozen, A. Pons, and J. A. Tur, “Worldwide consumption of functional foods: a systematic review,” Nutrition Reviews, vol. 70, no. 8, pp. 472–481, 2012.
View at: Publisher Site | Google Scholar
G. S. Jensen, X. Wu, K. M. Patterson et al., “In vitro and in vivo antioxidant and anti-inflammatory capacities of an antioxidant-rich fruit and berry juice blend. Results of a pilot and randomized, double-blinded, placebo-controlled, crossover study,” Journal of Agricultural and Food Chemistry, vol. 56, no. 18, pp. 8326–8333, 2008.
View at: Publisher Site | Google Scholar
J.-K. Lin and S.-Y. Lin-Shiau, “Mechanisms of hypolipidemic and anti-obesity effects of tea and tea polyphenols,” Molecular Nutrition & Food Research, vol. 50, no. 2, pp. 211–217, 2006.
View at: Publisher Site | Google Scholar
G. Tipoe, T.-M. Leung, M.-W. Hung, and M.-L. Fung, “Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection,” Cardiovascular & Hematological Disorders-Drug Targets, vol. 7, no. 2, pp. 135–144, 2007.
View at: Publisher Site | Google Scholar
S. Wang, J. P. Melnyk, R. Tsao, and M. F. Marcone, “How natural dietary antioxidants in fruits, vegetables and legumes promote vascular health,” Food Research International, vol. 44, no. 1, pp. 14–22, 2011.
View at: Publisher Site | Google Scholar
K. Griffiths, B. Aggarwal, R. Singh, H. Buttar, D. Wilson, and F. De Meester, “Food antioxidants and their anti-inflammatory properties: a potential role in cardiovascular diseases and cancer prevention,” Diseases, vol. 4, no. 4, p. 28, 2016.
View at: Publisher Site | Google Scholar
D. Aune, “Plant foods, antioxidant biomarkers, and the risk of cardiovascular disease, cancer, and mortality: a review of the evidence,” Advances in Nutrition, vol. 10, no. 4, pp. S404–S421, 2019.
View at: Publisher Site | Google Scholar
M. U. H. Joardder and M. Hasan Masud, “Causes of food waste,” in Food Preservation in Developing Countries: Challenges and Solutions, pp. 27–55, Springer International Publishing, Berlin, Germany, 2019.
View at: Publisher Site | Google Scholar
M. Eriksson, I. Strid, and P.-A. Hansson, “Food losses in six Swedish retail stores: wastage of fruit and vegetables in relation to quantities delivered,” Resources, Conservation and Recycling, vol. 68, pp. 14–20, 2012.
View at: Publisher Site | Google Scholar
A. O. Adebayo-Oyetoro, E. Adenubi, O. O. Ogundipe, B. O. Bankole, and S. A. O. Adeyeye, “Production and quality evaluation of vinegar from mango,” Cogent Food & Agriculture, vol. 3, no. 1, pp. 1–8, 2017.
View at: Publisher Site | Google Scholar
I. F. James, AD03E Preservation of Fruit and Vegetables, Agromisa Foundation, Wageningen, The Netherlands, 2003.
W. V. Cruess, Vinegar from Waste Fruits, Read Books Ltd., Redditch, UK, 2016.
R. B. Saper, D. M. Eisenberg, and R. S. Phillips, “Common dietary supplements for weight loss,” American Family Physician, vol. 70, no. 9, pp. 1731–1738, 2004.
View at: Google Scholar
F. Shahidi, J. McDonald, A. Chandrasekara, and Y. Zhong, “Phytochemicals of foods, beverages and fruit vinegars: chemistry and health effects,” Asia Pacific Journal of Clinical Nutrition, vol. 17, no. 1, pp. 380–382, 2008.
View at: Google Scholar
J. Ahn, H. Lee, S. Kim, J. Park, and T. Ha, “The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways,” Biochemical and Biophysical Research Communications, vol. 373, no. 4, pp. 545–549, 2008.
View at: Publisher Site | Google Scholar
R. F. Grimble, “Nutritional antioxidants and the modulation of inflammation: theory and practice,” New Horizons (Baltimore, Md.), vol. 2, no. 2, pp. 175–185, 1994.
View at: Google Scholar
J.-H. Lee, H.-D. Cho, J.-H. Jeong et al., “New vinegar produced by tomato suppresses adipocyte differentiation and fat accumulation in 3T3-L1 cells and obese rat model,” Food Chemistry, vol. 141, no. 3, pp. 3241–3249, 2013.
View at: Publisher Site | Google Scholar
K.-I. Seo, J. Lee, R.-Y. Choi et al., “Anti-obesity and anti-insulin resistance effects of tomato vinegar beverage in diet-induced obese mice,” Food & Function, vol. 5, no. 7, pp. 1579–1586, 2014.
View at: Publisher Site | Google Scholar
A. D’Introno, A. Paradiso, E. Scoditti et al., “Antioxidant and anti-inflammatory properties of tomato fruits synthesizing different amounts of stilbenes,” Plant Biotechnology Journal, vol. 7, no. 5, pp. 422–429, 2009.
View at: Publisher Site | Google Scholar
I. Martínez-Valverde, M. J. Periago, G. Provan, and A. Chesson, “Phenolic compounds, lycopene and antioxidant activity in commercial varieties of tomato (Lycopersicum esculentum),” Journal of the Science of Food and Agriculture, vol. 82, no. 3, pp. 323–330, 2002.
View at: Publisher Site | Google Scholar
N. E. Mohamad, S. K. Yeap, H. Ky et al., “Dietary coconut water vinegar for improvement of obesity-associated inflammation in high-fat-diet-treated mice,” Food & Nutrition Research, vol. 61, no. 1, Article ID 1368322, 2017.
View at: Publisher Site | Google Scholar
B. K. Beh, N. E. Mohamad, S. K. Yeap et al., “Anti-obesity and anti-inflammatory effects of synthetic acetic acid vinegar and nipa vinegar on high-fat-diet-induced obese mice,” Scientific Reports, vol. 7, no. 1, Article ID 6664, 2017.
View at: Publisher Site | Google Scholar
M. A. Hossain and S. M. M. Rahman, “Total phenolics, flavonoids and antioxidant activity of tropical fruit pineapple,” Food Research International, vol. 44, no. 3, pp. 672–676, 2011.
View at: Publisher Site | Google Scholar
T. Li, P. Shen, W. Liu et al., “Major polyphenolics in pineapple peels and their antioxidant interactions,” International Journal of Food Properties, vol. 17, no. 8, pp. 1805–1817, 2014.
View at: Publisher Site | Google Scholar
M. Majeed and K. Borole, “Evaluation of anti-inflammatory effect of pineapple juice in rheumatoid arthritis and osteoarthritis models in rats,” International Journal of Medical and Health Sciences, vol. 4, no. 1, pp. 70–76, 2015.
View at: Google Scholar
N. E. Mohamad, S. K. Yeap, K. L. Lim et al., “Antioxidant effects of pineapple vinegar in reversing of paracetamol-induced liver damage in mice,” Chinese Medicine, vol. 10, no. 1, pp. 1–14, 2015.
View at: Publisher Site | Google Scholar
G. Ambrosini, D. Johns, K. Northstone, and S. Jebb, “Fat, sugar or both ? A prospective analysis of dietary patterns and adiposity in children,” FASEB Journal, vol. 29, pp. 744–746, 2015.
View at: Google Scholar
A. Chalut-Carpentier, Z. Pataky, A. Golay, and E. Bobbioni-Harsch, “Involvement of dietary fatty acids in multiple biological and psychological functions, in morbidly obese subjects,” Obesity Surgery, vol. 25, no. 6, pp. 1031–1038, 2015.
View at: Publisher Site | Google Scholar
T. Deng, C. J. Lyon, S. Bergin, M. A. Caligiuri, and W. A. Hsueh, “Obesity, inflammation, and cancer,,” Annual Review of Pathology: Mechanisms of Disease, vol. 11, no. 1, pp. 421–449, 2016.
View at: Publisher Site | Google Scholar
W. Ruf and F. Samad, “Tissue factor pathways linking obesity and inflammation,” Hämostaseologie, vol. 35, no. 3, pp. 279–283, 2015.
View at: Publisher Site | Google Scholar
J. de Dios Lozano, B. I. Juárez-Flores, J. M. Pinos-Rodríguez, J. R. Aguirre-Rivera, and G. Álvarez-Fuentes, “Supplementary effects of vinegar on body weight and blood metabolites in healthy rats fed conventional diets and obese rats fed high-caloric diets,” Journal of Medicinal Plants Research, vol. 6, no. 24, pp. 4135–4141, 2012.
View at: Publisher Site | Google Scholar
S. Lim, J. W. Yoon, S. H. Choi et al., “Effect of ginsam, a vinegar extract from Panax ginseng, on body weight and glucose homeostasis in an obese insulin-resistant rat model,” Metabolism, vol. 58, no. 1, pp. 8–15, 2009.
View at: Publisher Site | Google Scholar
Y.-J. Moon, D.-S. Choi, S.-H. Oh, Y.-S. Song, and Y.-S. Cha, “Effects of persimmon-vinegar on lipid and carnitine profiles in mice,” Food Science and Biotechnology, vol. 19, no. 2, pp. 343–348, 2010.
View at: Publisher Site | Google Scholar
R. Eljaoudi, D. Elkabbaj, A. Bahadi, A. Ibrahimi, M. Benyahia, and M. Errasfa, “Consumption of argan oil improves anti-oxidant and lipid status in hemodialysis patients,” Phytotherapy Research, vol. 29, no. 10, pp. 1595–1599, 2015.
View at: Publisher Site | Google Scholar
S. Lakkur, S. Judd, R. M. Bostick et al., “Oxidative stress, inflammation, and markers of cardiovascular health,” Atherosclerosis, vol. 243, no. 1, pp. 38–43, 2015.
View at: Publisher Site | Google Scholar
Y. Zhang, K. E. Fischer, V. Soto et al., “Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice,” Archives of Biochemistry and Biophysics, vol. 576, pp. 39–48, 2015.
View at: Publisher Site | Google Scholar
R. K. Singh, B. Gupta, K. Tripathi, and S. K. Singh, “Anti oxidant potential of metformin and pioglitazone in type 2 diabetes mellitus: beyond their anti glycemic effect,” Diabetes & Metabolic Syndrome: Clinical Research & Reviews, vol. 10, no. 2, pp. 102–104, 2016.
View at: Publisher Site | Google Scholar
S. Cuzzocrea, C. Thiemermann, and D. Salvemini, “Potential therapeutic effect of antioxidant therapy in shock and inflammation,” Current Medicinal Chemistry, vol. 11, no. 9, pp. 1147–1162, 2004.
View at: Publisher Site | Google Scholar
J. M. Peake, K. Suzuki, and J. S. Coombes, “The influence of antioxidant supplementation on markers of inflammation and the relationship to oxidative stress after exercise,” The Journal of Nutritional Biochemistry, vol. 18, no. 6, pp. 357–371, 2007.
View at: Publisher Site | Google Scholar
Y.-Y. Chen, P.-C. Lee, Y.-L. Wu, and L.-Y. Liu, “In vivo effects of free form astaxanthin powder on anti-oxidation and lipid metabolism with high-cholesterol diet,” PLoS One, vol. 10, no. 8, Article ID e0134733, 2015.
View at: Publisher Site | Google Scholar
J. Taira, E. Tsuchida, M. C. Katoh, M. Uehara, and T. Ogi, “Antioxidant capacity of betacyanins as radical scavengers for peroxyl radical and nitric oxide,” Food Chemistry, vol. 166, pp. 531–536, 2015.
View at: Publisher Site | Google Scholar
B. B. Kahn and J. S. Flier, “Obesity and insulin resistance,” Journal of Clinical Investigation, vol. 106, no. 4, pp. 473–481, 2000.
View at: Publisher Site | Google Scholar
E. D. Abel, O. Peroni, J. K. Kim et al., “Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver,” Nature, vol. 409, no. 6821, pp. 729–733, 2001.
View at: Publisher Site | Google Scholar
R. J. Havel, V. G. Shore, B. Shore, and D. M. Bier, “Role of specific glycopeptides of human serum lipoproteins in the activation of lipoprotein lipase,” Circulation Research, vol. 27, no. 4, pp. 595–600, 1970.
View at: Publisher Site | Google Scholar
T. Yamauchi, J. Kamon, Y. Minokoshi et al., “Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase,” Nature Medicine, vol. 8, no. 11, pp. 1288–1295, 2002.
View at: Publisher Site | Google Scholar
A. M. Xydakis, C. C. Case, P. H. Jones et al., “Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction,” The Journal of Clinical Endocrinology & Metabolism, vol. 89, no. 6, pp. 2697–2703, 2004.
View at: Publisher Site | Google Scholar
J. D. Horton, J. L. Goldstein, and M. S. Brown, “SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver,” Journal of Clinical Investigation, vol. 109, no. 9, pp. 1125–1131, 2002.
View at: Publisher Site | Google Scholar
M. Watanabe, S. M. Houten, L. Wang et al., “Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c,” Journal of Clinical Investigation, vol. 113, no. 10, pp. 1408–1418, 2004.
View at: Publisher Site | Google Scholar
Y. Tao, V. Pinzi, J. Bourhis, and E. Deutsch, “Mechanisms of disease: signaling of the insulin-like growth factor 1 receptor pathway-therapeutic perspectives in cancer,” Nature Clinical Practice Oncology, vol. 4, no. 10, pp. 591–602, 2007.
View at: Publisher Site | Google Scholar
J. Nakae, Y. Kido, and D. Accili, “Distinct and overlapping functions of insulin and IGF-I receptors,” Endocrine Reviews, vol. 22, no. 6, pp. 818–835, 2001.
View at: Publisher Site | Google Scholar
R. Hernandez, T. Teruel, and M. Lorenzo, “Akt mediates insulin induction of glucose uptake and up-regulation of GLUT4 gene expression in brown adipocytes,” FEBS Letters, vol. 494, no. 3, pp. 225–231, 2001.
View at: Publisher Site | Google Scholar
G. Camenisch, M. T. Pisabarro, D. Sherman et al., “ANGPTL3 stimulates endothelial cell adhesion and migration via integrin αvβ3 and induces blood vessel formation in vivo,” Journal of Biological Chemistry, vol. 277, no. 19, pp. 17281–17290, 2002.
View at: Publisher Site | Google Scholar
M. Shimamura, M. Matsuda, S. Kobayashi et al., “Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes,” Biochemical and Biophysical Research Communications, vol. 301, no. 2, pp. 604–609, 2003.
View at: Publisher Site | Google Scholar
K. Fujimoto, R. Koishi, T. Shimizugawa, and Y. Ando, “Angptl3-null mice show low plasma lipid concentrations by enhanced lipoprotein lipase activity,” Experimental Animals, vol. 55, no. 1, pp. 27–34, 2006.
View at: Publisher Site | Google Scholar
M. R. Robciuc, M. Maranghi, A. Lahikainen et al., “Angptl3 deficiency is associated with increased insulin sensitivity, lipoprotein lipase activity, and decreased serum free fatty acids,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 7, pp. 1706–1713, 2013.
View at: Publisher Site | Google Scholar
T. Shimizugawa, M. Ono, M. Shimamura et al., “ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of lipoprotein lipase,” Journal of Biological Chemistry, vol. 277, no. 37, pp. 33742–33748, 2002.
View at: Publisher Site | Google Scholar
C. Bogardus, S. Lillioja, B. V. Howard, G. Reaven, and D. Mott, “Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects,” Journal of Clinical Investigation, vol. 74, no. 4, pp. 1238–1246, 1984.
View at: Publisher Site | Google Scholar
A. Vella, G. Bock, P. D. Giesler et al., “Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes,” Diabetes, vol. 56, no. 5, pp. 1475–1480, 2007.
View at: Publisher Site | Google Scholar
D. J. Drucker and M. A. Nauck, “The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes,” The Lancet, vol. 368, no. 9548, pp. 1696–1705, 2006.
View at: Publisher Site | Google Scholar
R. Lugari, A. Dei Cas, D. Ugolotti et al., “Glucagon-like peptide 1 (GLP-1) secretion and plasma dipeptidyl peptidase IV (DPP-IV) activity in morbidly obese patients undergoing biliopancreatic diversion,” Hormone and Metabolic Research, vol. 36, no. 2, pp. 111–115, 2004.
View at: Google Scholar
Q. Yang, T. E. Graham, N. Mody et al., “Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes,” Nature, vol. 436, no. 7049, pp. 356–362, 2005.
View at: Publisher Site | Google Scholar
M. C. Arkan, A. L. Hevener, F. R. Greten et al., “IKK-β links inflammation to obesity-induced insulin resistance,” Nature Medicine, vol. 11, no. 2, pp. 191–198, 2005.
View at: Publisher Site | Google Scholar
K. E. Wellen and G. S. Hotamisligil, “Obesity-induced inflammatory changes in adipose tissue,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1785–1788, 2003.
View at: Publisher Site | Google Scholar
M. Hämäläinen, R. Nieminen, P. Vuorela, M. Heinonen, and E. Moilanen, “Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-κB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages,” Mediators of Inflammation, vol. 2007, Article ID 045673, 10 pages, 2007.
View at: Publisher Site | Google Scholar
Y. Yamamoto and R. B. Gaynor, “Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer,” Journal of Clinical Investigation, vol. 107, no. 2, pp. 135–142, 2001.
View at: Publisher Site | Google Scholar
D. C. W. Lau, B. Dhillon, H. Yan, P. E. Szmitko, and S. Verma, “Adipokines: molecular links between obesity and atheroslcerosis,” American Journal of Physiology-Heart and Circulatory Physiology, vol. 288, no. 5, pp. H2031–H2041, 2005.
View at: Publisher Site | Google Scholar
M. Owecki, E. Nikisch, A. Miczke, D. Pupek-Musialik, and J. Sowiński, “Serum resistin is related to plasma HDL cholesterol and inversely correlated with LDL cholesterol in diabetic and obese humans,” Neuro Endocrinology Letters, vol. 31, no. 5, pp. 673–678, 2010.
View at: Google Scholar
C. Rae, S. A. Robertson, J. M. W. Taylor, and A. Graham, “Resistin induces lipolysis and re-esterification of triacylglycerol stores, and increases cholesteryl ester deposition, in human macrophages,” FEBS Letters, vol. 581, no. 25, pp. 4877–4883, 2007.
View at: Publisher Site | Google Scholar
P. M. Ridker, C. H. Hennekens, J. E. Buring, and N. Rifai, “C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women,” New England Journal of Medicine, vol. 342, no. 12, pp. 836–843, 2000.
View at: Publisher Site | Google Scholar
P. D. Cani, R. Bibiloni, C. Knauf et al., “Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice,” Diabetes, vol. 57, no. 6, pp. 1470–1481, 2008.
View at: Publisher Site | Google Scholar
P. Gérard, “Gut microbiota and obesity,” Cellular and Molecular Life Sciences, vol. 73, no. 1, pp. 147–162, 2016.
View at: Publisher Site | Google Scholar
N. Chaudhary, A. K. Sharma, P. Agarwal, A. Gupta, and V. K. Sharma, “16S classifier: a tool for fast and accurate taxonomic classification of 16S rRNA hypervariable regions in metagenomic datasets,” PLoS One, vol. 10, no. 2, Article ID e0116106, 2015.
View at: Publisher Site | Google Scholar
M. C. Dao, A. Everard, J. Aron-Wisnewsky et al., “Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology,” Gut, vol. 65, no. 3, pp. 426–436, 2015.
View at: Publisher Site | Google Scholar
D. E. Roopchand, R. N. Carmody, P. Kuhn et al., “Dietary polyphenols promote growth of the gut Bacterium Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome,” Diabetes, vol. 64, no. 8, pp. 2847–2858, 2015.
View at: Publisher Site | Google Scholar
M.-C. Cheng, T.-Y. Tsai, and T.-M. Pan, “Anti-obesity activity of the water extract of Lactobacillus paracasei subsp. paracasei NTU 101 fermented soy milk products,” Food & Function, vol. 6, no. 11, pp. 3522–3530, 2015.
View at: Publisher Site | Google Scholar
L. Bervoets, K. Van Hoorenbeeck, I. Kortleven et al., “Differences in gut microbiota composition between obese and lean children: a cross-sectional study,” Gut Pathogens, vol. 5, no. 1, pp. 1–10, 2013.
View at: Publisher Site | Google Scholar
Y. Sanz, R. Rastmanesh, and C. Agostonic, “Understanding the role of gut microbes and probiotics in obesity: how far are we?” Pharmacological Research, vol. 69, no. 1, pp. 144–155, 2013.
View at: Publisher Site | Google Scholar
S. C. Sopha, A. Manejwala, and C. N. Boutros, “Sarcina, a new threat in the bariatric era,” Human Pathology, vol. 46, no. 9, pp. 1405–1407, 2015.
View at: Publisher Site | Google Scholar
R. Pavan, S. Jain, A. Shraddha, and A. Kumar, “Properties and therapeutic application of bromelain: a review,” Biotechnology Research International, vol. 2012, Article ID 976203, 6 pages, 2012.
View at: Publisher Site | Google Scholar

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