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  • Synergetic Effects of Prenatal and Postnatal High Sucrose Intake on Glucose Tolerance and Hepatic Insulin Resistance in Rat Offspring
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-18
    Pengjie Zhang, Di Zhu, Yueming Zhang, Lingjun Li, Xionghui Chen, Wenna Zhang, Ruixiu Shi, Jianying Tao, Bing Han, Zhice Xu

    Scope : High sucrose intake during pregnancy is linked to type 2 diabetes mellitus and altered insulin resistance. Methods and results : This study attempted to ascertain whether prenatal high sucrose intake (20% sucrose) alleviates the detrimental effects of high postnatal sugar consumption in the offspring, and the molecular mechanisms were investigated using a rat model. High prenatal sucrose exposure increased the body weight of the offspring at 1 to 3 weeks of age. Exposure to both prenatal and postnatal high sucrose increased glucose tolerance in the 4-month-old adult offspring compared with offspring receiving other treatments. Postnatal high sucrose exposure suppressed food intake but increased the total daily caloric and fluid intake. Both fasting blood glucose and plasma triglyceride levels were increased, but the fasting insulin level was unaffected. Prenatal high sucrose intake enlarged pancreatic islet area; however, prenatal-plus-postnatal high sucrose exposure induced smaller pancreatic islets. IRS-1(S612) protein phosphorylation was significantly increased, and the GSK-3β (S9) phosphorylation level was reduced. Conclusion : Both prenatal and prenatal-plus-postnatal high sucrose exposure substantially affected biological functions related to insulin homeostasis. IRS-1(S612) protein phosphorylation appears to be a part of the molecular mechanism underlying these effects. These results add to the understanding of how high sucrose intake contributes to insulin resistance and diabetes pathogenesis and how postnatal nutrition and lifestyle may mitigate detrimental prenatal exposures. This article is protected by copyright. All rights reserved

    更新日期:2018-01-19
  • Allyl Isothiocyanate Ameliorates Obesity by Inhibiting Galectin-12
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-18
    Chia-Wen Lo, Chih-Sheng Chen, Ying-Chi Chen, Yu-An Hsu, Chi-Chun Huang, Ching-Yao Chang, Chao-Jen Lin, Cheng-Wen Lin, Hui-Ju Lin, Fu-Tong Liu, Lei Wan

    Scope : The aim of this study was to investigate the signaling pathways by which allyl isothiocyanate (AITC) reduces adipocyte differentiation and the efficacy of AITC in suppressing galectin-12 levels as a therapeutic for high fat diet (HFD)-induced obesity. Methods and results : AITC presents anti-adipogenic effects on 3T3-L1 cells by decreasing lipid droplet accumulation in a dose-dependent manner. AITC suppresses 3T3-L1 differentiation into adipocytes by decreasing galectin-12 expression and by down-regulating key adipogenic transcription factors. AITC influences the expression of 3T3-L1 pre-adipocytes by modulating adipokine expression (leptin and resistin) and by regulating the protein kinase B (PKB/Akt)/cAMP response element-binding protein (CREB) pathway. In HFD-fed mice, oral administration of AITC reduced the body weight, accumulation of lipid droplets in the liver, and white adipocyte size. Conclusion : In summary, our results indicate that AITC inhibits adipocyte differentiation by suppressing galectin-12 levels in 3T3L1 cells and has anti-obesity effects in HFD-fed mice. This article is protected by copyright. All rights reserved

    更新日期:2018-01-18
  • Kudingcha and Fuzhuan Brick Tea Prevent Obesity and Modulate Gut Microbiota in High-Fat Diet Fed Mice
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-18
    Guijie Chen, Minhao Xie, Zhuqing Dai, Peng Wan, Hong Ye, Xiaoxiong Zeng, Yi Sun

    Abstract Scope Kudingcha (KDC) from Ilex kudingcha and Fuzhuan brick tea (FBT) are popular beverages in China, and their preventive and therapeutic roles in metabolic disorders have been reported. However, the relationship between the gut microbiota modulatory effects of KDC and FBT and prevention of obesity is still not clearly understood. Methods and results KDC and FBT were tested individually for their capacities to prevent obesity and modulate the gut microbiota in high-fat diet (HFD) fed C57BL/6J mice. The results showed that both KDC and FBT supplementation could modulate oxidative injury, inflammation, lipid metabolism and reduce HFD induced obesity significantly. Both KDC and FBT could enhance the diversity of gut microbiota. KDC could reduce the relative abundance of Erysipelotrichaceae, while FBT could reduce the ratio of Firmicutes to Bacteroidetes and enhance the relative abundance of Bifidobacteriaceae. Conclusion These findings suggest that KDC and FBT could attenuate features of the metabolic syndrome in HFD-fed mice, which might be due to the modulation of gut microbiota by KDC and FBT. This article is protected by copyright. All rights reserved

    更新日期:2018-01-18
  • Resveratrol Influences Pancreatic Islets by Opposing Effects on Electrical Activity and Insulin Release
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-17
    Simone Brouwer, Theresa Hoffmeister, Anne Gresch, Lisa Schönhoff, Martina Düfer

    Abstract Scope Resveratrol is suggested to improve glycemic control by activation of sirtuin 1 (SIRT1) and has already been tested clinically. Our investigation characterizes the targets of resveratrol in pancreatic beta cells and their contribution to short- and long-term effects on insulin secretion. Methods and results Islets or beta cells were isolated from C57Bl/6N mice. Electrophysiology was performed with microelectrode arrays and patch-clamp technique, insulin secretion and content were determined by radioimmunoassay, cAMP was measured by enzyme-linked immunosorbent assay and cytosolic Ca2+ concentration by fluorescence methods. Resveratrol (25 μmol/L) elevated [Ca2+]c and potentiated glucose-stimulated insulin secretion. These effects were associated with increased intracellular cAMP and were sensitive to the SIRT1 blocker Ex-527. Inhibition of EPAC1 by CE3F4 also abolished the stimulatory effect of resveratrol. The underlying mechanism did not involve membrane depolarization as resveratrol even reduced electrical activity despite blocking KATP channels. Importantly, after prolonged exposure to resveratrol (14 days), the beneficial influence of the polyphenol on insulin release was lost. Conclusion Resveratrol addresses multiple targets in pancreatic islets. Potentiation of insulin secretion is mediated by SIRT1-dependent activation of cAMP/EPAC1. Considering resveratrol as therapeutic supplement for patients with type 2 diabetes mellitus, the inhibitory influence on electrical excitability attenuates positive effects. This article is protected by copyright. All rights reserved

    更新日期:2018-01-17
  • Stachyose Improves Inflammation Through Modulating Gut Microbiota of High-Fat Diet / Streptozotocin Induced Type 2 Diabetes in Rats
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-16
    Guimei Liu, Jia Bei, Li Liang, Guoyong Yu, Lu Li, Quanhong Li

    Abstract Scope The present study was undertaken to assess the effects of stachyose (STS) on type 2 diabetes in rats, and changes in the gut microbiota compared to metformin (MET). Methods and results The type 2 diabetic model was successfully established via a high-fat diet (HFD) / streptozotocin (STZ) in Wistar rats, and STS or MET was administered for 4 weeks. Blood was collected to analyze biochemical parameters, pancreas for mRNA expression of related gene and contents of colon for gut microbiota. STS or MET decreased serum lipopolysaccharide (LPS), mRNA expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, STS and MET showed a similar shifting of the structure of the gut microbiota, and a selective enrichment of key species. At the genus level, STS showed selective enrichment of Phascolarctobacterium, Bilophila, Oscillospira, Turicibacter and SMB5, but MET demonstrated a selective effect on Sutterella, Prevotella, 02d06 and rc4. The correlation analysis indicated that STS and MET decrease IL-6 and TNF-α and increase Akt/PI3K expression which were relative to key species of gut microbiota. Conclusion STS decreased pancreatic mRNA expression of IL-6 and TNF-α via key species of gut microbiota. The mechanism of this effect was similar to that of MET. This article is protected by copyright. All rights reserved

    更新日期:2018-01-17
  • Human Intestinal Dendritic Cells in Inflammatory Bowel Diseases
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-16
    David Bernardo, María Chaparro, Javier P Gisbert

    Abstract Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a serious, costly and persistent health problem with an estimated prevalence in Western countries around 0.5% of the general population; its socioeconomic impact is comparable with that for chronic diseases such as diabetes. Conventional treatment involves escalating drug regimens with concomitant side effects followed, in some cases, by surgical interventions which are often multiple, mainly in Crohn's disease. The goal of finding a targeted gut-specific immunotherapy for IBD patients is therefore an important unmet need. However, to achieve this goal we first must understand how dendritic cells (DC), the most potent antigen present cells of the immune system, control the immune tolerance in the gastrointestinal tract and how their properties are altered in those patients suffering from IBD. In this review, we summarize therefore the current available information regarding human intestinal DC subsets composition, phenotype and function in the human gastrointestinal tract describing how, in the IBD mucosa, DC display pro-inflammatory properties which drive disease progression. A better understanding of the mechanisms inducing DC abnormal profile in IBD may provide us therefore with novel tools to perform tissue specific immunomodulation. This article is protected by copyright. All rights reserved

    更新日期:2018-01-16
  • Human Milk Oligosaccharides as Promising Antivirals
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-16
    Vasily Morozov, Grant Hansman, Franz-Georg Hanisch, Horst Schroten, Clemens Kunz

    Abstract Human milk oligosaccharides (HMOs) are diverse unconjugated carbohydrates that are highly abundant in human breast milk. These glycans are investigated in the context of exhibiting multiple functions in infant growth and development. They seem to provide protection against infectious diseases, including a number of poorly manageable viral infections. Although the potential mechanism of the HMO antiviral protection is rather broad, much of the current experimental work has focused on studying of HMO antiadhesive properties. HMOs may mimic structures of viral receptors and block adherence to target cells, thus preventing infection. Still, the potential of HMOs as a source for new antiviral drugs is relatively unexploited. This can be partly attributed to the extreme complexity of the virus-carbohydrate interactions and technical difficulties in HMO isolation, characterization and manufacturing procedures. Fortunately, we are currently entering a period of major technological advances that have enabled deeper insights into carbohydrate mediated viral entry, rational selection of HMOs as anti-entry inhibitors, and even evaluation of individual synthetic HMO structures. Here, we provide an up-to-date review on glycan binding studies for rotaviruses, noroviruses, influenza viruses, and human immunodeficiency viruses. We also discuss the preventive and therapeutic potential of HMOs as anti-entry inhibitors and address challenges on the route from fundamental studies to clinical trials. This article is protected by copyright. All rights reserved

    更新日期:2018-01-16
  • Resveratrol Potently Counteracts Quercetin Starvation-Induced Autophagy and Sensitizes HepG2 Cancer Cells to Apoptosis
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-16
    Sarah Tomas-Hernández, Jordi Blanco, Cristina Rojas, Joel Roca-Martínez, María José Ojeda-Montes, Raúl Beltrán-Debón, Santiago Garcia-Vallve, Gerard Pujadas, Lluís Arola, Miquel Mulero

    Abstract Scope Resveratrol (RSV) has been described as a potent antioxidant, anti-steatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we tested the combined effect of QCT and RSV on the autophagy process in HepG2 cells Methods and results Autophagy was studied by western blotting, real-time RT-PCR, and cellular staining. Our results clearly indicate a bifunctional molecular effect of RSV. Both polyphenols were individually able to promote autophagy. Strikingly, when RSV was combined with QCT, it promoted a potent reduction of QCT-induced autophagy and influenced pro-apoptotic signaling. Conclusion RSV acts differentially on the autophagic process depending on the cellular energetic state. We further characterized the molecular mechanisms related to this effect, and we observed that AMP-activated protein kinase (AMPK) phosphorylation, heme oxygenase 1 (HO-1) downregulation, lysosomal membrane permeabilization (LMP) and Zinc (Zn2+) dynamics could be important modulators of such RSV-related effects and could globally represent a promising strategy to sensitize cancer cells to QCT treatment. This article is protected by copyright. All rights reserved

    更新日期:2018-01-16
  • Highly Dispersible and Bioavailable Curcumin but not Native Curcumin Induces Brown-Like Adipocyte Formation in Mice
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-15
    Sho Nishikawa, Misa Kamiya, Hiroki Aoyama, Mami Nomura, Takuma Hyodo, Aoi Ozeki, Hyunjin Lee, Tsukasa Takahashi, Atsushi Imaizumi, Takanori Tsuda

    Scope : The induction of brown-like adipocytes in white adipose tissue (WAT) is a potential therapeutic target for the treatment of obesity and metabolic disorders via the ability of these cells to release excess energy as heat in association with uncoupling protein 1. Some experimental trials suggest that curcumin (a yellow pigment from turmeric) has a suppressive effect on the accumulation of body fat. However, there is little evidence to show that curcumin induces the formation of brown-like adipocytes and the molecular mechanisms involved remain elusive. In addition, in most experimental trials, high doses of curcumin are administered. Methods and results : Highly dispersible and bioavailable curcumin (HC, i.e., 4.5 mg native curcumin/kg) but not the same dose of native curcumin induces the formation of brown-like adipocytes in mouse inguinal WAT. Moreover, the formation of brown-like adipocytes induced by HC in inguinal WAT may be mediated by the production of local norepinephrine from accumulated alternatively activated macrophages. Conclusion : These novel findings suggested that curcumin increased energy expenditure by inducing the formation of brown-like adipocytes via a unique molecular mechanism. Importantly, they showed that HC has significant bioactive effects in vivo at lower doses of curcumin. This article is protected by copyright. All rights reserved

    更新日期:2018-01-15
  • Lactic Acid Bacteria may Impact Intestinal Barrier Function by Modulating Goblet Cells
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-15
    Chengcheng Ren, Jelleke Dokter-Fokkens, Susana Figueroa Lozano, Qiuxiang Zhang, Bart J. Haan, Hao Zhang, Marijke M. Faas, Paul Vos

    Scope : Lactic acid bacteria (LAB) are recognized to promote gastrointestinal health by mechanisms that are not fully understood. LABs might modulate the mucus and thereby enhance intestinal barrier function. Herein, we investigated effects of different LAB strains and species on goblet cell genes involved in mucus synthesis. Methods and results : Gene expression profiles of goblet cell-associated products (mucin MUC2, trefoil factor 3, resistin-like molecule β, carbohydrate sulfotransferase 5, and galactose-3-O-sulfotransferase 2) induced by LAB or their derived conditioned medium in human goblet cell line LS174T were studied. Effects of LAB on gene transcription were assessed with or without exposure to TNF-α, IL-13 or the mucus damaging agent tunicamycin. LAB did impact the related genes in a species and strain specific fashion and their effects were different in the presence of the cytokines and tunicamycin. Bioactive factors secreted by some strains were also found to regulate goblet cell-related genes. Conclusion : Our findings provide novel insights in differences in modulatory efficacy on mucus genes between LAB species and strains. This study further unravels direct interactions between LAB and intestinal goblet cells, and highlights the importance of rationally selecting appropriate LAB candidates to achieve specific benefits in the gut. This article is protected by copyright. All rights reserved

    更新日期:2018-01-15
  • Dietary Factors Modulate Colonic Tumorigenesis Through the Interaction of Gut Microbiota and Host Chloride Channels
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-13
    Yong Zhang, Chao Kang, Xiao-lan Wang, Min Zhou, Meng-ting Chen, Xiao-hui Zhu, Kai Liu, Bin Wang, Qian-yong Zhang, Jun-dong Zhu, Man-tian Mi

    Scope : In recent decades, the association between diet, gut microbiota and the risk of colorectal cancer (CRC) has been established. Gut microbiota and associated metabolites, such as bile acids and butyrate, are now known to play a key role in CRC development. The aim of this study was to identify the progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat diet or different dose of dihydromyricetin (DMY) interacted with gut microbiota. Methods and results : An AOM/DSS (azoxymethan/dextran sodium sulfate) model was established to study the gut microbiota compsition before and after tumor formation during colitis-induced tumorigenesis. All above dietary factors profoundly influenced the composition of gut microbiota and host colonic tumorigenesis. In addition, mice with DMY-modified initial microbiota displayed different degrees of chemically-induced tumorigenesis. Mechanism analysis revealed that gut microbiota-associated chloride channels participated in colon tumorigenesis. Conclusion : Gut microbiota changes occured in the hyperproliferative stage before tumor formation. Gut microbiota and host chloride channels, both of which are regulated by dietary factors, are associated with CRC development. This article is protected by copyright. All rights reserved

    更新日期:2018-01-13
  • Obesity Impairs Oligopeptide/Amino Acid-Induced Ghrelin Release and Smooth Muscle Contractions in the Human Proximal Stomach
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-11
    L Vancleef, T Thijs, F Baert, L J Ceulemans, E Canovai, Q Wang, S Steensels, A Segers, R Farré, J Pirenne, M Lannoo, J Tack, I Depoortere

    Scope The satiation properties of proteins involve effects on gut peptide release and gastrointestinal motility which may be altered during obesity. This study compared the in vitro response and role of amino acid (AA) taste receptors (TASR) in the effect of AAs and a casein hydrolysate on ghrelin release and smooth muscle (SM) contractions in the proximal gut of lean and obese patients. Methods and results Basal ghrelin release, measured from mucosal segments, was maximal in the fundus and decreased distally. Obesity selectively impaired the stimulatory effect of a casein hydrolyaste on ghrelin release in the fundus but did not affect its inhibitory effect in the small intestine (SI). The SM contractions induced by a casein hydrolysate and AAs were stronger in strips from the SI than from the fundus but were reduced in the stomach of obese patients. The region-dependent expression of AA-TASRs in the mucosa and SM layer was affected by obesity. Most of the AA-induced responses were reduced by the umami antagonist, lactisole. L-Met-induced responses involved bitter taste receptors. Conclusion Region-specific targeting of AA taste receptors on both enteroendocrine and SM cells with specific AA-enriched diets might be a useful strategy to combat obesity as well as hypomotility disorders. This article is protected by copyright. All rights reserved

    更新日期:2018-01-12
  • Rice Protein Matrix Enhances Circulating Levels of Xanthohumol Following Acute Oral Intake of Spent Hops in Humans
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-11
    Annalouise O'Connor, Veera Konda, Ralph L. Reed, J. Mark Christensen, Jan F. Stevens, Nikhat Contractor

    Scope: Xanthohumol (XN), a prenylated flavonoid found in hops, exhibits anti-inflammatory and antioxidant properties. However, poor bioavailability may limit therapeutic applications. As food components are known to modulate polyphenol absorption, the objective was to determine whether a protein matrix could enhance the bioavailability of XN post oral consumption in humans.Methods and results: This was a randomized, double-blind, cross-over study in healthy participants (n = 6) evaluating XN and its major metabolites [isoxanthohumol (IX), 6- and 8-prenylnaringenin (6-PN, 8-PN)] for 6 hours following consumption of 12.4 mg of XN delivered via a spent hops-rice protein matrix preparation or a control spent hops preparation. Plasma XN and metabolites were measured by LC-MS/MS. Cmax, Tmax, and area-under-the-curve (AUC) values were determined. Circulating XN and metabolite response to each treatment was not bioequivalent. Plasma concentrations of XN and XN + metabolites (AUC) were greater with consumption of the spent hops-rice protein matrix preparation.Conclusion: Compared to a standard spent hops powder, a protein-rich spent hops matrix demonstrates enhanced plasma levels of XN and metabolites following acute oral intake.This article is protected by copyright. All rights reserved

    更新日期:2018-01-11
  • Raspberry Supplementation Improves Insulin Signaling and Promotes Brown-Like Adipocyte Development in White Adipose Tissue of Obese Mice
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-10
    Tong Xing, Yifei Kang, Xinglian Xu, Bo Wang, Min Du, Mei-Jun Zhu

    Scope: Excessive lipid accumulation in white adipose tissue (WAT) leads to chronic inflammation and metabolic dysfunction. Raspberry (RB) contains high amount of polyphenolics and dietary fibers. The objective of the study is to evaluate effects of RB supplementation on WAT morphology, inflammation and insulin signaling in high fat diet (HFD)-induced obese mice, and further explore the underlying mechanisms.Methods and results: C57BL/6J mice were fed with a control diet or a HFD supplemented with 0 or 5% freeze dried RB for 12 weeks. RB supplementation decreased WAT hypertrophy induced by HFD and suppressed pro-inflammatory cytokines expression and macrophage infiltration in WAT. Meanwhile, RB addition improved insulin sensitivity of HFD-mice. Additionally, RB supplementation drove the browning of WAT (beige adipogenesis), which was associated with elevated PGC-1α and FNDC5/irisin contents. Consistently, the content of beige adipocyte markers including UCP1, PRDM16, Cytochrome C, Cidea and Elvol3 was enhanced in HFD-mice, which were correlated with increased AMPK phosphorylation and Sirt1 protein contents.Conclusion: Dietary RB attenuated adipocyte hypertrophy and inflammation of WAT in HFD-mice and improved insulin sensitivity and beige adipogenesis, which is associated with increased FNDC5/irisin content and activation of AMPK/Sirt1 pathway. RB supplementation provides a promising strategy to prevent diet-induced obesity.This article is protected by copyright. All rights reserved

    更新日期:2018-01-11
  • 更新日期:2018-01-10
  • Back Cover: Regulation of Hedgehog Signaling in Cancer by Natural and Dietary Compounds
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-10
    Cheng Bao, Pavel Kramata, Hong Jin Lee, Nanjoo Suh
    更新日期:2018-01-10
  • Naringin Protects Pancreatic β-Cells Against Oxidative Stress-Induced Apoptosis by Inhibiting Both Intrinsic and Extrinsic Pathways in Insulin-Deficient Diabetic Mice
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-04
    Ye Jin Lim, Jung Ho Kim, Jeong Hoon Pan, Jae Kyeom Kim, Tae-Sik Park, Young Jun Kim, Jin Hyup Lee, Jun Ho Kim

    Scope : Oxidative stress has been suggested to play a central role in the pathogenesis of diabetes, as well as other metabolic disorders. Naringin, a major flavanone glycoside in citrus species, has been shown to display strong antioxidant potential in in vitro and in vivo models of oxidative stress; however, the underlying protective mechanisms in diabetes are unclear. Methods and results : To study the protective effects and molecular mechanisms of naringin in preventing islet dysfunction and diabetes, we examined glucose homeostasis, β-cell apoptosis, and inflammatory response in insulin-deficient diabetic mice exposed to acute oxidative stress with streptozotocin (STZ). Naringin dose-dependently ameliorated hyperglycemia and islet dysfunction in insulin-deficient diabetic mice. Naringin counteracted STZ-induced β-cell apoptosis by inhibiting both the intrinsic (mitochondria-mediated) and extrinsic (death receptor-mediated) pathways. Furthermore, these protective effects were associated with suppression of DNA damage response and nuclear factor–kappa B (NF–κB)– and mitogen–activated protein kinase (MAPK)–mediated signaling pathways, as well as reduction of reactive oxygen species accumulation and proinflammatory cytokine production in the pancreas. Conclusion : Taken together, our study provides insights into the underlying mechanisms through which naringin protects the pancreatic β-cells against oxidative stress-induced apoptosis. This article is protected by copyright. All rights reserved

    更新日期:2018-01-04
  • Extracellular Vesicles from Hypoxic Adipocytes and obese subjects reduce Insulin-Stimulated Glucose Uptake
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2018-01-02
    Justyna Mleczko, Francisco J. Ortega, Juan Manuel Falcon-Perez, Martin Wabitsch, Jose Manuel Fernandez-Real, Silvia Mora

    Scope: We investigated the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness.Methods and results: EVs were isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen) or exposed to macrophage conditioned media (15%v/v). EVs were isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes were incubated with EVs and activation of insulin signalling cascades and insulin-stimulated glucose transport were measured. EVs released from hypoxic adipocytes impaired insulin-stimulated 2-deoxyglucose uptake and reduced insulin mediate phosphorylation of AKT. Insulin-mediated phosphorylation of extracellular regulated kinases (ERK1/2) was not affected. EVs from individuals with obesity decreased insulin stimulated 2-deoxyglucose uptake in adipocytes (p = 0.0159).Conclusion: Extracellular vesicles released by stressed adipocytes impair insulin action in neighbouring adipocytes.This article is protected by copyright. All rights reserved

    更新日期:2018-01-02
  • Isothiocyanates and Xenobiotic Detoxification
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-30
    Ahmad Faizal Abdull Razis, Nattaya Konsue, Costas Ioannides

    Abstract The potential of isothiocyanates to antagonise the carcinogenicity of structurally-diverse chemicals has been established in animals. A feasible mechanism of action involves protecting DNA by reducing the availability of the genotoxic metabolites of chemical carcinogens by either inhibiting their generation and/or stimulating their detoxification. In vivo as well as in vitro studies conducted in rat/human primary hepatocytes and precision-cut tissue slices have revealed that isothiocyanates can impair cytochrome P450 activity, including the CYP1 family which is the most active in the bioactivation of carcinogens, by virtue of being mechanism-based inactivators. The aromatic phenethyl isothiocyanate is the most effective of those studied, whereas aliphatic isothiocyanates such as sulforaphane and erucin necessitate high doses in order to manifest such effects that may not always be achievable through the diet. In all systems studied, isothiocyanates are strong inducers of detoxification enzyme systems including quinone reductase, glutathione S-transferase, epoxide hydrolase and UDP-glucuronosyl transferase. Indeed, in smokers phenethyl isothiocyanate intake increased the urinary excretion of inactive mercapturate metabolites of toxic chemicals present in tobacco. Glucosinolates, the precursors of isothiocyanates, have also the potential to up-regulate detoxification enzyme systems, but their contribution to the cancer chemoprevention linked to cruciferous vegetable consumption remains to be evaluated. This article is protected by copyright. All rights reserved

    更新日期:2017-12-31
  • A Novel Anti-Hypertensive Peptide Identified in Thermolysin-Digested Rice Bran
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-27
    Naohisa Shobako, Yutaro Ogawa, Atsushi Ishikado, Kayo Harada, Etsuko Kobayashi, Hirohisa Suido, Takeshi Kusakari, Mariko Maeda, Makoto Suwa, Motonobu Matsumoto, Ryuhei Kanamoto, Kousaku Ohinata

    Scope: Hypertension is a risk factor for arteriosclerosis. In this study, we investigated the anti-hypertensive effect of protease-digested rice bran in a spontaneously hypertension rat (SHR) model. We also purified a novel anti-hypertensive peptide from the digest.Methods and results: Thermolysin-digested rice bran (TRB) was administered to SHRs for 4 weeks, and systolic blood pressure (SBP) was measured weekly using the tail-cuff method. TRB showed an anti-hypertensive effect in a dose-dependent manner. TRB also reduced angiotensin I-converting enzyme (ACE) activity in lung tissue and serum troponin I levels. TRB was fractionated by high-performance liquid chromatography (HPLC) and ACE-inhibitory activity in the HPLC fractions was measured. Peptides LRA and YY were identified from the two fractions with the strongest ACE-inhibitory activity. Amino acid sequence of these peptides were found in a vicilin-like seed storage protein, and identified in rice bran protein using the peptide mass fingerprint method. We confirmed that LRA and YY were cleaved by thermolysin digestion of a model synthetic peptide. Orally administered LRA (0.25 mg/kg) or YY (0.5 mg/kg) lowered the SBP of SHRs at 4 h after administration.Conclusion: We identified a novel, orally active anti-hypertensive peptide, LRA from the digest of rice bran protein.This article is protected by copyright. All rights reserved

    更新日期:2017-12-27
  • Bioavailable Blueberry-Derived Phenolic Acids at Physiological Concentrations Enhance Nrf2-Regulated Antioxidant Responses in Human Vascular Endothelial Cells
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-26
    Jeffry S. Tang, Margreet C. M. Vissers, Robert F. Anderson, Sreevalsan Sreebhavan, Stephanie. M. Bozonet, Arjan Scheepens, Laurence D. Melton

    Scope : Blueberry consumption is believed to confer a cardiovascular health advantage, but the active compounds and effects require characterization. This study aimed to identify the polyphenol metabolites in plasma after blueberry juice intake and determine their bioactivity on endothelial cells. Methods and results : Three healthy individuals were recruited to obtain profiles of bioavailable plasma polyphenol metabolites following intake of blueberry juice. Of 33 phenolic compounds screened, 12 aglycone phenolic acids were detected and their maximum plasma concentrations and circulation time determined. Using this information, the effect of three physiologically-relevant mixtures of blueberry-derived phenolic acids were investigated for their ability to induce Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-nuclear translocation and downstream gene expression in human endothelial cells. Pre-treatment with the phenolic acids for 18 h resulted in a significant up-regulation of the Nrf2-regulated antioxidant response proteins heme oxygenase 1 (HO-1) and glutamate-cysteine ligase modifier subunit (GCLM), following 6 h exposure to 2.5 μM H2O2. Conclusion : Physiologically-relevant concentrations of blueberry-derived aglycone phenolic acids can induce Nrf2-regulated antioxidant response proteins in vascular endothelial cells in response to low μM concentrations of H2O2. Our results represent an advance over previous studies that have used single compounds or high concentrations in cell-based investigations. This article is protected by copyright. All rights reserved

    更新日期:2017-12-27
  • Green Tea Polyphenol EGCG Alleviates Metabolic Abnormality and Fatty Liver by Decreasing Bile Acid and Lipid Absorption in Mice
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-26
    Jinbao Huang, Simin Feng, Anna Liu, Zhuqing Dai, Hong Wang, Kenneth Reuhl, Wenyun Lu, Chung S. Yang

    Abstract Scope The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been shown to ameliorate metabolic abnormalities and fatty liver. The present study investigated the mechanisms of actions of EGCG on bile acid homeostasis and lipid metabolism. Methods Male C57BL/6J mice were fed a low-fat diet, a high-fat western-style diet or a high-fat western-style diet containing 0.32% EGCG. The effects of the treatments on biochemical parameters, gene expression and lipidomics were analyzed. Results EGCG treatment significantly reduced body weight gain, mesenteric fat mass, fasting blood glucose, insulin resistance, serum cholesterol and severity of fatty liver after treatment for 17 weeks, but most of these effects were less apparent at week 33. At week 17, EGCG treatment significantly elevated the mRNA levels of cholesterol 7α-hydroxylase, HMG-CoA reductase, low-density lipoprotein receptor and scavenger receptor B1, and partially normalized the high-fat diet induced lipidomic profile. The intestinal bile acid content was significantly decreased by EGCG, while fecal excretion of bile acids, cholesterol and total lipids were increased. Conclusion EGCG decreases bile acid reabsorption, results in lower intestinal bile acid levels, which further decreased the absorption of lipids. These actions contribute to the alleviation of metabolic abnormalities and fatty liver disease caused by the high-fat diet. This article is protected by copyright. All rights reserved

    更新日期:2017-12-27
  • Egg White Ovotransferrin-Derived ACE inhibitory Peptide Ameliorates Angiotensin II-Stimulated Insulin Resistance in Skeletal Muscle Cells
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-26
    Myoungjin Son, Catherine B. Chan, Jianping Wu

    Scope : The renin-angiotensin system (RAS) is a major contributor to the development of insulin resistance and its related complications. Egg white ovotransferrin-derived tripeptides, IRW, IQW, or LKP were previously identified as the inhibitors of angiotensin converting enzyme (ACE), a key enzyme in the RAS. This study aimed at determining whether these peptides are effective in improving insulin resistance, and their mechanisms of action, in a rat derived skeletal muscle cell line (L6 cells). Methods and results : Insulin resistance was induced by treating L6 cells with 1 μM angiotensin II (Ang II) for 24 h. Effects of peptides on glucose uptake were determined using glucose uptake assay, glucose transporter 4 (GLUT4) translocation by immunofluorescence, reactive oxygen species (ROS) by dihydroethidium (DHE) staining, while insulin signaling pathway, Ang II receptor (AT1R or AT2R) levels and NADPH oxidase activation were measured using Western Blot. Only IRW treatment significantly improved insulin resistance in L6 cells via stimulation of insulin signaling. IRW decreased Ang II-stimulated AT1R expression, ROS formation and NADPH oxidase activation. Conclusions : Of three ACE inhibitory peptides studied, only IRW improved insulin resistance in L6 cells, at least partially via reduced AT1R expression and its anti-oxidative activity. This article is protected by copyright. All rights reserved

    更新日期:2017-12-27
  • Intake of Fish Oil Specifically Modulates Colonic Muc2 Expression in Middle-Aged Rats by Suppressing the Glycosylation Process
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-26
    Yafang Ma, Guanghong Zhou, Yingqiu Li, Yingying Zhu, Xiaobo Yu, Fan Zhao, He Li, Xinglian Xu, Chunbao Li

    Abstract Scope Dietary fats have been shown to affect gut microbiota composition and aging gene expression of middle-aged rats at a normal dose, but little is known about such an effect on gut barrier. In this study, the changes in colonic Muc2 expression were investigated and the underlying mechanism was also proposed. Methods and results Thirty-six middle-aged Sprague-Dawley rats were assigned to one of diets containing soybean oil, lard or fish oil (4%). The rats were fed for 5 weeks and then goblet cells, Muc2 expression and inflammatory cytokines in the colon were measured. Proteome analysis was performed. Compared with the lard and soybean oil diet groups, intake of fish oil decreased the number of goblet cells, and inhibited Muc2 and TLRs expression in the colon of middle-aged rats, which would impair mucus barrier. Several key enzymes involved in glycosylation process, including Agr2, Gale, Gne, Pmm2, Pdxdc1, Plch1, Pfkp, Cmpk1 and Rexo2, showed the lowest abundance in the fish oil diet group. Conclusion Intake of fish oil at a normal dose downregulated colonic Muc2 expression. This negative effect of fish oil may involve the suppression of mucin glycosylation process. This article is protected by copyright. All rights reserved

    更新日期:2017-12-27
  • Thymoquinone Can Improve Neuronal Survival and Promote Neurogenesis in Rat Hippocampal Neurons
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-26
    Merve Beker, Tuğçe Dallı, Birsen Elibol

    Abstract Scope Thymoquinone (TQ) has been used as a potential therapeutic for diseases such as cancer, and diabetes. Herein, we aimed to investigate the effect of TQ on behavioral and molecular parameters in healthy rat hippocampus. Methods TQ (20 mg/kg/day) was administered intragastrically for 15 days to adult rats. After the behavioral tests, the hippocampal tissues were investigated in histological and molecular level. Results In both DG and CA1, TQ significantly increased the number of hippocampal neurons. This increase was supported by a significant increase in the doublecortin expression on both gene and protein levels. In addition, TQ significantly decreased the amount of Caspase-3 expression and the cleavage of PARP indicating a decrease in apoptosis. Further, ERK, GSK-3, JNK, CREB, and iNOS proteins were found to be positively regulated by TQ. However, the gene expression of synapsin, synaptophysin, NGF, AKT, Bax, NFkB and p53 and the protein expression of BDNF and nNOS were not affected by TQ. Conclusion These findings suggest that TQ has an enhancing effect on cell survival and neurogenesis in healthy hippocampus rather inducing apoptosis in damaged neurons. This may proceed via ERK/JNK and CREB signaling pathways as a candidate acting mechanism for TQ. This article is protected by copyright. All rights reserved

    更新日期:2017-12-27
  • Camelina Sativa Oil, but not Fatty Fish or Lean Fish Improved Serum Lipid Profile in Subjects with Impaired Glucose Metabolism – a Randomized Controlled Trial
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-22
    Ursula S. Schwab, Maria A. Lankinen, Vanessa D. Mello, Suvi M. Manninen, Sudhir Kurl, Kari J. Pulkki, David E. Laaksonen, Arja T. Erkkilä

    Scope : The aim of the study was to examine whether lean fish (LF), fatty fish (FF) and camelina sativa oil (CSO), a plant-based source of alpha-linolenic acid (ALA), differ in their metabolic effects in subjects with impaired glucose metabolism. Methods and results : Altogether 79 volunteers with impaired fasting glucose, BMI 25–36 kg/m2, age 43–72 years, participated in a 12-week randomized controlled trial with four parallel groups, i.e. the FF (4 fish meals/week), LF (4 fish meals/week), CSO (10 g/day ALA) and control (limited intakes of fish and source of ALA) groups. The proportions of EPA and DHA increased in plasma lipids in the FF group, and the proportion of ALA increased in the CSO group (P < 0.0001 for all). In the CSO group total and LDL-cholesterol (C) concentrations decreased compared with the FF and LF groups, LDL-C/HDL-C and ApoB/ApoA-I ratios decreased compared with the LF group. There were no significant changes in glucose metabolism or markers of low-grade inflammation. Conclusions : A diet enriched in CSO improves serum lipid profile as compared with a diet enriched in FF or LF in subjects with impaired fasting glucose, with no differences in glucose metabolism or concentrations of inflammatory markers. This article is protected by copyright. All rights reserved

    更新日期:2017-12-22
  • The Hypotriglyceridemic Effect of Sciadonic Acid is Mediated by the Inhibition of Δ9-Desaturase Expression and Activity
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-22
    Frédérique Pédrono, Nathalie Boulier-Monthéan, Françoise Boissel, Jordane Ossemond, Françoise Lohézic-Le Dévéhat

    Scope : Sciadonic acid (Scia; 20:3Δ5,11,14) is a distinctive fatty acid (FA) with a polymethylene-interrupted double bond at C5. It is specifically found in seeds from gymnosperms such as pine nuts. Published papers describe a decrease in liver and plasma triacylglycerols in rats fed with this nutriment. The present study sought to identify the action mechanism of Scia on triacylglycerol synthesis. In this way, its nutritional effect on FA metabolism involving the Stearoyl-CoA Desaturase 1 (SCD1) was investigated. Methods and results : Scia was discerned in trace amount in various tissues of rats and in human serum. It was produced by Δ5-desaturation of 20:2n-6 in human transfected SH-SY5Y cell lines and also in rat hepatocytes. When Scia was incubated with cultured hepatocytes as a nutrient, the cellular FA profile was modified. In particular, the proportion of the monoenes (18:1n-9, 18:1n-7, 16:1n-7) were all decreased, correlating to the reduction of triacylglycerol amounts. This effect was mediated by the inhibition of SCD1 expression. Furthermore, Scia, as well as 20:3n-6 and 20:3n-9 but not 20:3n-3, strongly inhibited the SCD1 activity measured on liver microsomes. Conclusion : Overall this study showed that Scia, despite its unusual structure, contributes to the FA metabolism and reduced triacylglycerol release by inhibiting SCD1 activity. This article is protected by copyright. All rights reserved

    更新日期:2017-12-22
  • The Efficacy of Nanoemulsion-Based Delivery to Improve Vitamin D Absorption: Comparison of in Vitro and in Vivo Studies
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-21
    Alagu Selvi Kadappan, Chi Guo, Cansu E. Gumus, Amy Bessey, Richard J. Wood, David J. McClements, Zhenhua Liu

    Abstract Scope Vitamin D (VD) is a fat-soluble vitamin that has a wide range of skeletal and non-skeletal functions. Although it can be synthesized through sun exposure and obtained from fortified foods, VD inadequacy is epidemic worldwide. Therefore innovative strategies are necessary for improving VD status. The present study examined VD absorption via nanoscale delivery systems. Methods and results We examined the physical characteristics and in vitro bioaccessibility of cholecalciferol (VD3) in nanoemulsion using a simulated gastrointestinal tract system. To evaluate the in vivo bioavailability, we orally administrated three groups of mice with VD3 nanoemulsion, VD3 coarse emulsion or vehicle nanoemulsion without VD3, and the serum 25(OH)D3 was measured using radioactive immunoassay. The nanoemulsion-based delivery system increased the in vitro bioaccessibility by 3.94 folds (p < 0.05) as indicated by the concentration of vitamin D3 in micelles. Our animal study showed that, when compared to the vehicle group, the coarse emulsion numerically increased the serum 25(OH)D3 by 36%, whereas the nanoemulsion statistically significantly increased the serum 25(OH)D3 by 73% (p < 0.01). Conclusion Our findings indicated that a nanoemulsion-based delivery system is a promising approach to improve VD bioavailability, and further studies are warranted to determine its efficacy in humans. This article is protected by copyright. All rights reserved

    更新日期:2017-12-21
  • Mediterranean Tomato-Based Sofrito Sauce Improves Fibroblast Growth Factor 21 (FGF21) Signaling in White Adipose Tissue of Obese ZUCKER Rats
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-21
    Viviana Sandoval, Rosalía Rodríguez-Rodríguez, Úrsula Martínez-Garza, Cristina Rosell-Cardona, Rosa Lamuela-Raventós, Pedro F. Marrero, Diego Haro, Joana Relat

    Scope : Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Since FGF21 production and signaling are regulated by some bioactive dietary compounds, we analyzed the impact of Mediterranean tomato-based sofrito sauce on: i) the FGF21 expression and signaling in visceral white adipose tissue (vWAT), and ii) the insulin sensitivity of obese Zucker rats (OZR). Methods and results : OZR were fed with a sofrito-supplemented diet or control diet. Insulin sensitivity and FGF21 signaling were determined. We observed that sofrito is able to improve the responsiveness to both hormones in obese rats. Sofrito-supplemented diet increased FGF21 signaling in vWAT by inducing the expression of the FGF receptors (FGFR1 and FGFR4) that promotes the expression of canonical target genes, like Egr-1, c-Fos and uncoupling protein 1 (Ucp1). Conclusions : A sofrito-supplemented diet improves insulin and FGF21 sensitivity in OZR, explaining part of sofrito’s healthy effects on glucose metabolism. In addition, induction of UCP1 and the unchanged body weight despite the hyperphagic behavior of the sofrito-fed rats suggests that the increase in FGF21 signaling correlates with an increase in energy expenditure (EE). Further studies in humans may help to understand whether sofrito consumption increases the EE in obese individuals. This article is protected by copyright. All rights reserved

    更新日期:2017-12-21
  • Vitamin A Deficiency Induces Autistic-Like Behaviors in Rats by Regulating the RARβ-CD38-Oxytocin Axis in the Hypothalamus
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-21
    Xi Lai, Xiaofeng Wu, Nali Hou, Shu Liu, Qing Li, Ting Yang, Jingkun Miao, Zhifang Dong, Jie Chen, Tingyu Li

    Scope : Vitamin A (VA) is an essential nutrient for the development of the brain. We previously found that children with autism spectrum disorder (ASD) have a significant rate of VA deficiency (VAD). In the current study, we aim to determine whether VAD is a risk factor for the generation of autistic-like behaviors via the transcription factor retinoic acid receptor beta (RARβ)-regulated cluster of differentiation 38 (CD38)-oxytocin (OXT) axis. Methods and results : Gestational VAD or VA supplementation (VAS) rat models were established, and the autistic-like behaviors in the offspring rats were investigated. The different expression levels of RARβ and CD38 in hypothalamic tissue and serum retinol and OXT concentration were tested. Primary cultured rat hypothalamic neurons were treated with all trans retinoic acid (atRA) and recombinant adenoviruses carrying the rat RARβ (AdRARβ) or RNA interference virus RARβ-siRNA (siRARβ) were used to infect neurons to change RARβ signal. Western blotting, chromatin immunoprecipitation (ChIP) and intracellular Ca2+ detections were used to investigate the primary regulatory mechanism of RARβ in the CD38-OXT signaling pathway. We found that gestational VAD increased autistic-like behaviors and decreased the expression levels of hypothalamic RARβ and CD38 and serum OXT levels in the offspring. VAS ameliorated these autistic-like behaviors and increased the expression levels of RARβ, CD38 and OXT in the gestational VAD pups. In vitro, atRA increased the Ca2+ excitability of neurons, which might further promote the release of OXT. Different CD38 levels were induced in the neurons by infection with different RARβ adenoviruses. Furthermore, atRA enhanced the binding of RARβ to the proximal promoter of CD38, indicating a potential up-regulation of CD38 transcriptional activity by RARβ. Conclusions : Gestational VAD might be a risk factor for autistic-like behaviors due to the RARβ signal suppression of CD38 expression in the hypothalamus of the offspring, which improved with VAS during the early-life period. The nutritional status during pregnancy and the early-life period is important in rats. This article is protected by copyright. All rights reserved

    更新日期:2017-12-21
  • Bioavailability of Glucoraphanin and Sulforaphane From High-Glucoraphanin Broccoli
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-21
    Tharsini Sivapalan, Antonietta Melchini, Shikha Saha, Paul W. Needs, Maria H. Traka, Henri Tapp, Jack R. Dainty, Richard F. Mithen

    Abstract Scope Broccoli accumulates 4-methylsulphinylbutyl glucosinolate (glucoraphanin) which is hydrolyzed to the isothiocyanate sulforaphane. Through the introgression of novel alleles of the Myb28 transcription factor from Brassica villosa, broccoli genotypes have been developed that have enhanced levels of glucoraphanin. This study sought to quantify the exposure of human tissues to glucoraphanin and sulforaphane following consumption of broccoli with contrasting Myb28 genotypes. Methods and results Ten participants were recruited into a three-phase, double-blinded, randomized crossover trial (NCT02300324), with each phase comprising consumption of 300 ml of a soup made from broccoli of one of three Myb28 genotypes (Myb28B/B, Myb28B/V, Myb28V/V). Plant myrosinases were intentionally denatured during soup manufacture. Three-fold and five-fold higher levels of sulforaphane occurred in the circulation following consumption of Myb28V/B and Myb28V/V broccoli soups, respectively. The percentage of sulforaphane excreted in 24 h relative to the amount of glucoraphanin consumed varied amongst volunteers from 2% to 15%, but did not depend on the broccoli genotype. Conclusion This is the first study to report the bioavailability of glucoraphanin and sulforaphane from soups made with novel broccoli varieties. The presence of one or two Myb28V alleles results in enhanced delivery of sulforaphane to the systemic circulation. This article is protected by copyright. All rights reserved

    更新日期:2017-12-21
  • Quercetin Attenuates Ethanol-Induced Iron Uptake and Myocardial Injury by Regulating the Angiotensin II-L-Type Calcium Channel
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-21
    Xiaoping Guo, Man Chen, Hongmei Zeng, Peiyi Liu, Xinghong Zhu, Feng Zhou, Jingjing Liu, Jun Zhang, Zhuangzhuang Dong, Yuhan Tang, Chao Gao, Ping Yao

    Abstract Scope Increased iron deposition in the myocardium in alcoholics may lead to increased risk of cardiac dysfunction. Quercetin has been demonstrated to quench production of intracellular free iron-induced ∙OH, but the effect of quercetin in ethanol-induced cardiac damage remains unclear. This study was to explore whether quercetin attenuates ethanol-induced iron uptake and myocardial injury by regulating Ang II-LTCC. Methods and results Adult male C57BL/6J mice were isocalorically pair-fed either a regular or ethanol-containing Lieber De Carli liquid diets supplemented with either quercetin (100 mg/kg.bw) or desferrioxamine mesylate (DFO, 100 mg/kg.bw) for 15 weeks. Quercetin alleviated ethanol-induced histopathological changes, CK-MB release, Ang II secretion, ROS generation, total cardiac iron and labile iron level. Ethanol exposure or quercetin intervention failed to regulate traditional iron transporters except LTCC. LTCC was upregulated by ethanol and inhibited by quercetin. In H9C2 cell, LTCC was increased by ethanol (100mM) and/or Ang II (1μM) concomitant with iron disorders and oxidative stress. This effect was partially normalized by quercetin (50 μM), nifedipine (LTCC inhibitor, 15 μM), or losartan (Ang II receptor antagonist, 100 μM). Conclusion Alcohol-induced cardiac injury was associated with excessive NTBI uptake mediated by Ang II-LTCC activation which may be mediated by quercetin against ethanol cardiotoxicity This article is protected by copyright. All rights reserved

    更新日期:2017-12-21
  • Tomato Powder Inhibits Hepatic Steatosis and Inflammation Potentially Through Restoring SIRT1 Activity and Adiponectin Function Independent of Carotenoid Cleavage Enzymes in Mice
    Mol. Nutr. Food Res. (IF 4.323) Pub Date : 2017-12-20
    Cheng-Chung Li, Chun Liu, Maobin Fu, Kang-Quan Hu, Koichi Aizawa, Shingo Takahashi, Suganuma Hiroyuki, Junrui Cheng, Johannes Lintig, Xiang-Dong Wang

    Abstract Scope Beta-carotene-15,15’-oxygenase (BCO1) and beta-carotene-9’,10’-oxygenase (BCO2) metabolize lycopene to biologically active metabolites, which can ameliorate nonalcoholic fatty liver disease (NAFLD). We investigated the effects of tomato powder (TP containing substantial lycopene (2.3 mg/g)) on NAFLD development and gut microbiome in the absence of both BCO1 and BCO2 in mice. Method and results BCO1−/−/BCO2−/− double knockout mice were fed a high fat diet (HFD) alone (n = 9) or with TP feeding (n = 9) for 24 weeks. TP feeding significantly reduced pathological severity of steatosis and hepatic triglyceride levels in BCO1−/−/BCO2−/− mice (P<0.04 vs. HFD alone). This was associated with increased SIRT1 activity, nicotinamide phosphoribosyltransferase expression and AMPK phosphorylation, and subsequently decreased lipogenesis, hepatic fatty acid uptake, and increasing fatty acid β-oxidation (P<0.05). TP feeding significantly decreased mRNA expression of pro-inflammatory genes (tnf-α, il-1β and il-6) in both liver and mesenteric adipose tissue, which were associated with increased plasma adiponectin and hepatic adiponectin receptor-2. Multiplexed 16S rRNA gene sequencing was performed using DNA extracted from cecum fecal samples. TP feeding increased microbial richness and decreased relative abundance of the genus Clostridium. Conclusion Dietary TP can inhibit NAFLD independent of carotenoid cleavage enzymes, potentially through increasing SIRT1 activity and adiponectin production and decreasing Clostridium abundance. This article is protected by copyright. All rights reserved

    更新日期:2017-12-20
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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