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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 May 2017) | Viewed by 79471

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Prof. Dr. Young-Joon Surh

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Guest Editor

Department of Molecular Medicine and Biopharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
Interests: medicinal phytochemicals; oxidative stress in cells; cancer chemoprevention; tumor microenvironment; signal transduction in inflammation and carcinogenesis

Dr. Hye-Kyung Na

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Guest Editor

Department of Food Science and Biotechnology, College of Knowledge-Based Service Engineering, Sungshin Women's University, Seoul 01133, Republic of Korea
Interests: cancer prevention; inflammation; antioxidant; alcohol metabolism; cancer; prostaglandin metabolism

Special Issue Information

Dear Colleagues,

This Special Issue contains a selection of papers presented at the Asia Pacific Nutrigenomics and Nutrigenetics Organisation (APNNO) Biennial Conference at Gyeongju, South Korea in December 2016. This Special Issue will highlight the following strategic subjects:

Nutrient-gene interaction
Epigenetic regulation by nutrients
Nutritional modulation of cancer and metabolic disorders
Effects of diet on inflammation-associated ailments
Role of gut microbiota in health and disease
Precision/personalized nutrition

Prof. Dr. Young-Joon Surh
Prof. Hye-Kyung Na
Guest Editors

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Published Papers (12 papers)

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1921 KiB

Open AccessArticle

Phyllodulcin, a Natural Sweetener, Regulates Obesity-Related Metabolic Changes and Fat Browning-Related Genes of Subcutaneous White Adipose Tissue in High-Fat Diet-Induced Obese Mice

by Eunju Kim, Soo-Min Lim, Min-Soo Kim, Sang-Ho Yoo and Yuri Kim

Nutrients 2017, 9(10), 1049; https://doi.org/10.3390/nu9101049 - 21 Sep 2017

Cited by 28 | Viewed by 8339

Abstract

Phyllodulcin is a natural sweetener found in Hydrangea macrophylla var. thunbergii. This study investigated whether phyllodulcin could improve metabolic abnormalities in high-fat diet (HFD)-induced obese mice. Animals were fed a 60% HFD for 6 weeks to induce obesity, followed by 7 weeks of supplementation with phyllodulcin (20 or 40 mg/kg body weight (b.w.)/day). Stevioside (40 mg/kg b.w./day) was used as a positive control. Phyllodulcin supplementation reduced subcutaneous fat mass, levels of plasma lipids, triglycerides, total cholesterol, and low-density lipoprotein cholesterol and improved the levels of leptin, adiponectin, and fasting blood glucose. In subcutaneous fat tissues, supplementation with stevioside or phyllodulcin significantly decreased mRNA expression of lipogenesis-related genes, including CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator activated receptor γ (PPARγ), and sterol regulatory element-binding protein-1C (SREBP-1c) compared to the high-fat group. Phyllodulcin supplementation significantly increased the expression of fat browning-related genes, including PR domain containing 16 (Prdm16), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), compared to the high-fat group. Hypothalamic brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) signaling was upregulated by phyllodulcin supplementation. In conclusion, phyllodulcin is a potential sweetener that could be used to combat obesity by regulating levels of leptin, fat browning-related genes, and hypothalamic BDNF-TrkB signaling. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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3013 KiB

Open AccessArticle

Oligonol, a Low-Molecular Weight Polyphenol Derived from Lychee, Alleviates Muscle Loss in Diabetes by Suppressing Atrogin-1 and MuRF1

by Hung-Wen Liu, Yen-Ju Chen, Yun-Ching Chang and Sue-Joan Chang

Nutrients 2017, 9(9), 1040; https://doi.org/10.3390/nu9091040 - 20 Sep 2017

Cited by 25 | Viewed by 10889

Abstract

Stimulation of the ubiquitin-proteasome pathway—especially E3 ubiquitin ligases Atrogin-1 and MuRF1—is associated with muscle loss in diabetes. Elevated lipid metabolites impair myogenesis. Oligonol, a low molecular weight polyphenol derived from lychee, exhibited anti-diabetic and anti-obesity properties, suggesting it could be a proper supplement for attenuating muscle loss. Dietary (10 weeks) oligonol supplementation (20 or 200 mg/kg diet) on the skeletal muscle loss was investigated in diabetic db/db mice. Transcription factors NF-κB and FoxO3a involved in regulation of Atrogin-1 and MuRF1 were also investigated. Attenuation of muscle loss by oligonol (both doses) was associated with down-regulation of Atrogin-1 and MuRF1 gene expression. Oligonol supplementation decreased NF-κB expression in the nuclear fraction compared with db/db mice without oligonol supplement. Upregulation of sirtuin1 (SIRT1) expression prevented FoxO3a nuclear localization in db/db mice supplemented with oligonol. Marked increases in AMPKα activity and Ppara mRNA expression leading to lower lipid accumulation by oligonol provided additional benefits for attenuating muscle loss. Oligonol limited palmitate-induced senescent phenotype and cell cycle arrest and suppressed Atrogin-1 and MuRF1 mRNA expression in palmitate-treated C2C12 muscle cells, thus contributing to improving the impaired myotube formation. In conclusion, oligonol-mediated downregulation of Atrogin-1 and MuRF1 gene expression alleviates muscle loss and improves the impaired myotube formation, indicating that oligonol supplementation may be useful for the attenuation of myotube loss. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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258 KiB

Open AccessArticle

Association and Interaction Effect of AGTR1 and AGTR2 Gene Polymorphisms with Dietary Pattern on Metabolic Risk Factors of Cardiovascular Disease in Malaysian Adults

by Roseline Wai Kuan Yap, Yoshihiro Shidoji, Wai Sum Yap and Motofumi Masaki

Nutrients 2017, 9(8), 853; https://doi.org/10.3390/nu9080853 - 09 Aug 2017

Cited by 19 | Viewed by 4611

Abstract

Gene-diet interaction using a multifactorial approach is preferred to study the multiple risk factors of cardiovascular disease (CVD). This study examined the association and gene-diet interaction effects of the angiotensin II type 1 receptor (AGTR1) gene (rs5186), and type 2 receptor (AGTR2) gene (rs1403543) polymorphisms on metabolic risk factors of CVD in Malaysian adults. CVD parameters (BMI, blood pressure, glycated hemoglobin, total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and TC/HDL-C ratio), and constructed dietary patterns “vegetables, fruits, and soy diet” (VFSD), and “rice, egg, and fish diet” (REFD) were obtained from previous studies. Genotyping analysis was performed by real-time PCR using Taqman probes. The subjects were 507 adults (151 Malays; 179 Chinese; and 177 Indians). Significant genetic associations were obtained on blood lipids for rs5186 in Malays and Chinese, and rs1403543 in Chinese females. The significant gene-diet interaction effects after adjusting for potential confounders were: rs5186 × VFSD on blood pressure in Malays (p = 0.016), and in Chinese on blood lipids for rs5186 × REFD (p = 0.009–0.023), and rs1403543 × VFSD in female subjects (p = 0.001–0.011). Malays and Chinese showed higher risk for blood pressure and/or lipids involving rs5186 and rs1403543 SNPs together with gene-diet interactions, but not Indians. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

618 KiB

Open AccessArticle

Effect of Red Ginseng on Genotoxicity and Health-Related Quality of Life after Adjuvant Chemotherapy in Patients with Epithelial Ovarian Cancer: A Randomized, Double Blind, Placebo-Controlled Trial

by Hee Seung Kim, Mi-Kyung Kim, Maria Lee, Byung-Su Kwon, Dong Hoon Suh and Yong Sang Song

Nutrients 2017, 9(7), 772; https://doi.org/10.3390/nu9070772 - 19 Jul 2017

Cited by 40 | Viewed by 6149

Abstract

We evaluated the effect of red ginseng on toxicity, health-related quality of life (HRQL) and survival after adjuvant chemotherapy in patients with epithelial ovarian cancer (EOC). A total of 30 patients with EOC were randomly assigned to placebo (n = 15) and red ginseng groups (n = 15). All patients took placebo or red ginseng (3000 mg/day) for three months. Then, we compared changes of genotoxicity, HRQL and survival between the two groups. As a result, red ginseng reduced micronuclei yield in comparison with placebo despite no difference of binucleated cells index. Although red ginseng increased serum levels of alanine aminotransferase and aspartate aminotransferase significantly, they were within the normal value. Moreover, there were no differences in adverse events between placebo and red ginseng groups. In terms of HRQL, red ginseng was associated with improved emotional functioning and decreased symptoms of fatigue, nausea and vomiting, and dyspnea, reduced anxiety and interference affecting life and improved daytime somnolence. However, there was no effect of red ginseng on prognosis of EOC. Conclusively, red ginseng may be safe and effective to reduce genotoxicity and improve HRQL despite no benefit of survival in patients with EOC who received chemotherapy. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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2946 KiB

Open AccessArticle

Suppression of Nrf2 Activity by Chestnut Leaf Extract Increases Chemosensitivity of Breast Cancer Stem Cells to Paclitaxel

by Yaejin Woo, Jisun Oh and Jong-Sang Kim

Nutrients 2017, 9(7), 760; https://doi.org/10.3390/nu9070760 - 18 Jul 2017

Cited by 46 | Viewed by 5830

Abstract

Due to metastatic potential and drug resistance, cancer stem cells (CSCs) have become a critical target for the development of chemotherapeutic agents. Recent studies showed that CSCs highly express NF-E2-related factor 2 (Nrf2)-mediated antioxidant enzymes and thereby retain relatively low levels of reactive oxygen species (ROS). Since anticancer agents usually utilize ROS as an arsenal for killing cancer cells, we hypothesized that inhibition of Nrf2 activity could increase the sensitivity of CSCs to anticancer drugs, and thus enhancing their therapeutic efficacy. We found that MCF-7-derived CSCs with a CD44^high/CD24^low phenotype formed mammospheres and highly expressed Nrf2 compared to the adherent parental MCF-7 cells. In a separate experiment, we screened 89 different edible plant extracts for inhibitory activity against the Nrf2 signaling pathway by using an antioxidant response element (ARE)-luciferase assay system. Among those extracts, Castanea crenata (chestnut) leaf extract significantly decreased the nuclear translocation of Nrf2 and protein expression of antioxidant enzymes in MCF-7-derived CSCs. The combined treatment of the CSCs with chestnut leaf extract and paclitaxel resulted in more effective cell death than the treatment with paclitaxel alone. These findings suggest that the chestnut leaf extract or its constituents could increase the susceptibility of breast CSCs to an anticancer drug, paclitaxel, through inhibition of the Nrf2 signaling pathway, and could be utilized as an adjuvant for chemotherapy. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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3321 KiB

Open AccessArticle

Docosahexaenoic Acid Inhibits Cerulein-Induced Acute Pancreatitis in Rats

by Yoo Kyung Jeong, Sle Lee, Joo Weon Lim and Hyeyoung Kim

Nutrients 2017, 9(7), 744; https://doi.org/10.3390/nu9070744 - 12 Jul 2017

Cited by 15 | Viewed by 4683

Abstract

Oxidative stress is an important regulator in the pathogenesis of acute pancreatitis (AP). Reactive oxygen species induce activation of inflammatory cascades, inflammatory cell recruitment, and tissue damage. NF-κB regulates inflammatory cytokine gene expression, which induces an acute, edematous form of pancreatitis. Protein kinase C δ (PKCδ) activates NF-κB as shown in a mouse model of cerulein-induced AP. Docosahexaenoic acid (DHA), an ω-3 fatty acid, exerts anti-inflammatory and antioxidant effects in various cells and tissues. This study investigated whether DHA inhibits cerulein-induced AP in rats by assessing pancreatic edema, myeloperoxidase activity, levels of lipid peroxide and IL-6, activation of NF-κB and PKCδ, and by histologic observation. AP was induced by intraperitoneal injection (i.p.) of cerulein (50 μg/kg) every hour for 7 h. DHA (13 mg/kg) was administered i.p. for three days before AP induction. Pretreatment with DHA reduced cerulein-induced activation of NF-κB, PKCδ, and IL-6 in pancreatic tissues of rats. DHA suppressed pancreatic edema and decreased the abundance of lipid peroxide, myeloperoxidase activity, and inflammatory cell infiltration into the pancreatic tissues of cerulein-stimulated rats. Therefore, DHA may help prevent the development of pancreatitis by suppressing the activation of NF-κB and PKCδ, expression of IL-6, and oxidative damage to the pancreas. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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350 KiB

Open AccessArticle

The Gene-Lifestyle Interaction on Leptin Sensitivity and Lipid Metabolism in Adults: A Population Based Study

by Harry Freitag Luglio, Dian Caturini Sulistyoningrum, Emy Huriyati, Yi Yi Lee and Wan Abdul Manan Wan Muda

Nutrients 2017, 9(7), 716; https://doi.org/10.3390/nu9070716 - 07 Jul 2017

Cited by 5 | Viewed by 4411

Abstract

Background: Obesity has been associated with leptin resistance and this might be caused by genetic factors. The aim of this study was to investigate the gene-lifestyle interaction between −866G/A UCP2 (uncoupling protein 2) gene polymorphism, dietary intake and leptin in a population based study. Methods: This is a cross sectional study conducted in adults living at urban area of Yogyakarta, Indonesia. Data of adiposity, lifestyle, triglyceride, high density lipoprotein (HDL) cholesterol, leptin and UCP2 gene polymorphism were obtained in 380 men and female adults. Results: UCP2 gene polymorphism was not significantly associated with adiposity, leptin, triglyceride, HDL cholesterol, dietary intake and physical activity (all p > 0.05). Leptin was lower in overweight subjects with AA + GA genotypes than those with GG genotype counterparts (p = 0.029). In subjects with AA + GA genotypes there was a negative correlation between leptin concentration (r = −0.324; p < 0.0001) and total energy intake and this correlation was not seen in GG genotype (r = −0.111; p = 0.188). Conclusions: In summary, we showed how genetic variation in −866G/A UCP2 affected individual response to leptin production. AA + GA genotype had a better leptin sensitivity shown by its response in dietary intake and body mass index (BMI) and this explained the protective effect of A allele to obesity. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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1543 KiB

Open AccessArticle

Quercetin Protects Obesity-Induced Hypothalamic Inflammation by Reducing Microglia-Mediated Inflammatory Responses via HO-1 Induction

by Jihyeon Yang, Chu-Sook Kim, Thai Hien Tu, Min-Seon Kim, Tsuyoshi Goto, Teruo Kawada, Myung-Sook Choi, Taesun Park, Mi-Kyung Sung, Jong Won Yun, Suck-Young Choe, Jee Hye Lee, Yeonsoo Joe, Hye-Seon Choi, Sung Hoon Back, Hun Taeg Chung and Rina Yu

Nutrients 2017, 9(7), 650; https://doi.org/10.3390/nu9070650 - 23 Jun 2017

Cited by 50 | Viewed by 7244

Abstract

Obesity-induced hypothalamic inflammation is characterized by activation of microglia, which are resident macrophages of the central nervous system, and is implicated in the derangement of energy homeostasis, metabolic complications, and neurodegenerative diseases. Quercetin, a naturally occurring flavonoid, is known to protect against oxidative stress and inflammation-related metabolic complications. Here, we demonstrate that quercetin reduces obesity-induced hypothalamic inflammation by inhibiting microglia-mediated inflammatory responses, and the beneficial action of quercetin is associated with heme oxygenase (HO-1) induction. Quercetin markedly reduced the production of inflammatory mediators (monocyte chemoattractant protein (MCP)-1, interleukin (IL-6), IL-1β, nitric oxide) by microglia stimulated with saturated fatty acid palmitate and/or lipid-laden microglia-conditioned medium. Quercetin also upregulated the expression of HO-1 in palmitate-treated lipid-laden microglia, and the actions of quercetin against microglia activation accompanied by IκBα degradation were abolished by a HO-1 inhibitor. Moreover, quercetin supplementation reduced the levels of inflammatory cytokines and microglia activation markers in the hypothalamus of high fat diet (HFD)-fed obese mice, which was accompanied by upregulation of HO-1. These findings indicate that quercetin suppresses microglia-mediated inflammatory responses via the induction of HO-1, and hence protects against obesity-induced hypothalamic inflammation. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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13764 KiB

Open AccessArticle

Zeolite-Containing Mixture Supplementation Ameliorated Dextran Sodium Sulfate-Induced Colitis in Mice by Suppressing the Inflammatory Bowel Disease Pathway and Improving Apoptosis in Colon Mucosa

by Weida Lyu, Huijuan Jia, Chuanzong Deng, Kenji Saito, Seigo Yamada and Hisanori Kato

Nutrients 2017, 9(5), 467; https://doi.org/10.3390/nu9050467 - 06 May 2017

Cited by 7 | Viewed by 5641

Abstract

Inflammatory bowel disease (IBD) is induced by multiple environmental factors, and there is still no known treatment capable of curing the disease completely. We propose a zeolite-containing mixture (Hydryeast^®, HY)—a multi-component nutraceutical of which the main ingredients are Azumaceramics (mixture of zeolite and oyster shell burned under high temperature), citric acid, red rice yeast (monascus) and calcium stearate—as a nutraceutical intervention in IBD to ameliorate dextran sodium sulfate (DSS)-induced colitis. We show the mechanism through integrated omics using transcriptomics and proteomics. C57BL6 mice were given an AIN-93G basal diet or a 0.8% HY containing diet and sterilized tap water for 11 days. Colitis was then induced by 1.5% (w/v) DSS-containing water for 9 days. HY fed mice showed significantly improved disease activity index and colon length compared to DSS mice. Colonic mucosa microarray analysis plus RT-PCR results indicate HY supplementation may ameliorate inflammation by inhibiting the intestinal inflammatory pathway and suppress apoptosis by curbing the expression of genes like tumor protein 53 and epidermal growth factor receptor and by upregulating epithelial protection-related proteins such as epithelial cell adhesion molecule and tenascin C, thus maintaining mucosal immune homeostasis and epithelial integrity, mirroring the proteome analysis results. HY appears to have a suppressive effect on colitis. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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419 KiB

Open AccessArticle

Genetic Risk Score of Nine Type 2 Diabetes Risk Variants that Interact with Erythrocyte Phospholipid Alpha-Linolenic Acid for Type 2 Diabetes in Chinese Hans: A Case-Control Study

by Ju-Sheng Zheng, Kelei Li, Tao Huang, Yanqiu Chen, Hua Xie, Danfeng Xu, Jianqin Sun and Duo Li

Nutrients 2017, 9(4), 376; https://doi.org/10.3390/nu9040376 - 11 Apr 2017

Cited by 13 | Viewed by 4231

Abstract

Modulation of n-3 fatty acids on genetic susceptibility to type 2 diabetes (T2D) is still not clear. In a case-control study of 622 Chinese T2D patients and 293 healthy controls, a genetic risk score (GRS) was created based on nine T2D genetic variants. Logistic regression was used to examine the interaction of the GRS with erythrocyte phospholipid n-3 fatty acids for T2D risk. Every 1-unit (corresponding to 1 risk allele) increase in GRS was associated with 12% (Odds ratio (OR): 1.12; 95% confidence intervals (CI): 1.04–1.20) higher risk of T2D. Compared with the lowest quartile, participants had lower T2D risk in the 2nd (OR: 0.55; 95% CI: 0.36–0.84), 3rd (OR: 0.58; 95% CI: 0.38–0.88) and 4th (OR: 0.67; 95% CI: 0.44–1.03) quartile of alpha-linolenic acid (ALA) levels. Significant interaction (p-interaction = 0.029) of GRS with ALA for T2D risk was observed. Higher ALA levels were associated with lower T2D risk only among participants within the lowest GRS tertile, with ORs 0.51 (95% CI: 0.26–1.03), 0.44 (95% CI: 0.22–0.89) and 0.49 (95% CI: 0.25–0.96) for the 2nd, 3rd and 4th ALA quartile, compared with the 1st. This study suggests that higher erythrocyte ALA levels are inversely associated with T2D risk only among participants with low T2D genetic risk, with high genetic risk abolishing the ALA-T2D association. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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Review

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832 KiB

Open AccessReview

Anti-Inflammatory Thioredoxin Family Proteins for Medicare, Healthcare and Aging Care

by Junji Yodoi, Yoshiyuki Matsuo, Hai Tian, Hiroshi Masutani and Takashi Inamoto

Nutrients 2017, 9(10), 1081; https://doi.org/10.3390/nu9101081 - 29 Sep 2017

Cited by 26 | Viewed by 6735

Abstract

Human thioredoxin (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-, which is induced by biological stress due to oxidative damage, metabolic dysfunction, chemicals, infection/inflammation, irradiation, or hypoxia/ischemia-reperfusion. Our research has demonstrated that exogenous TRX is effective in a wide variety of inflammatory diseases, including viral pneumonia, acute lung injury, gastric injury, and dermatitis, as well as in the prevention and amelioration of food allergies. Preclinical and clinical studies using recombinant TRX (rhTRX) are now underway. We have also identified substances that induce the expression of TRX in the body, in vegetables and other plant ingredients. Skincare products are being developed that take advantage of the anti-inflammatory and anti-allergic action of TRX. Furthermore, we are currently engaged in the highly efficient production of pure rhTRX in several plants, such as lettuce, grain and rice. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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606 KiB

Open AccessReview

Personalised Interventions—A Precision Approach for the Next Generation of Dietary Intervention Studies

by Baukje De Roos and Lorraine Brennan

Nutrients 2017, 9(8), 847; https://doi.org/10.3390/nu9080847 - 09 Aug 2017

Cited by 52 | Viewed by 9661

Abstract

Diet is a key modifiable risk factor for non-communicable diseases. However, we currently are not benefitting from the full potential of its protective effects. This is due to a number of reasons, including high individual variability in response to certain diets. It is now well acknowledged that in order to gain the full benefit of dietary regimes it is essential to take into account individual responses. With this in mind, the present review examines the concept of precision nutrition and the performance of n-of-1 studies, and discusses the development of certain approaches that will be critical for development of the concepts. Full article

(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)

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