Kun Xie, Satoshi Yano, Jinyun Wang, Shota Yamakoshi, Tomoe Ohta, Takuhiro Uto, Maiko Sakai, Xi He, Kaichi Yoshizaki, Takumi Kubota, Kohta Ohnishi, Taichi Hara
{"title":"The Yeast-Fermented Garlic and a Balance of Spermine/Spermidine Activates Autophagy via EGR1 Transcriptional Factor","authors":"Kun Xie, Satoshi Yano, Jinyun Wang, Shota Yamakoshi, Tomoe Ohta, Takuhiro Uto, Maiko Sakai, Xi He, Kaichi Yoshizaki, Takumi Kubota, Kohta Ohnishi, Taichi Hara","doi":"10.1002/mnfr.202400606","DOIUrl":"10.1002/mnfr.202400606","url":null,"abstract":"<p>Spermine (SPM) and spermidine (SPD) are polyamines found in all organisms, and their concentrations can be regulated by ingestion. We demonstrated that yeast-fermented garlic (YF) extract significantly increased autophag flux in OUMS-36T-1 and HeLa cells expressing the fluorescent probe (GFP-LC3-RFP-LC3ΔG). YF-induced increase of autophagy occurred independently of mTORC1 signaling, and RNA-sequencing analysis revealed that <i>EGR1</i> was the most significantly altered gene in YF-treated OUMS-36T-1 cells. YF-treated <i>EGR1-</i>deficient HAP1 cells displayed reduced autophagic flux (<i>p </i>< 0.05). YF-induced increasing of autophagic flux occurred via a specific SPM/SPD ratio. HAP1 cells treated with equivalent amounts of SPD or SPM as that found in YF did not increase autophagic flux (<i>p</i> > 0.05); however, treatment with SPD and SPM in the same ratio as that found in YF increased autophagic flux (<i>p</i> < 0.05). This specific SPM/SPD ratio reduced MG132-induced proteostress via <i>EGR1</i>-dependent pathways (<i>p</i> < 0.05). Thus, the SPM/SPD balance may regulate autophagy via <i>EGR1</i>-dependent pathways, and controlling this balance may provide a strategy to maintain cellular homeostasis.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.202400606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan Yang, Hai-Xia Xu, Wen-Jun Wang, Zhong-Ping Yin, Ji-Guang Chen, En Yuan, Qing-Feng Zhang
{"title":"Roselle Extract Ameliorates Abnormal Glucolipid Metabolism and Gut Microbiota in Obese Mice Fed With High-Fat Diet","authors":"Dan Yang, Hai-Xia Xu, Wen-Jun Wang, Zhong-Ping Yin, Ji-Guang Chen, En Yuan, Qing-Feng Zhang","doi":"10.1002/mnfr.202400756","DOIUrl":"10.1002/mnfr.202400756","url":null,"abstract":"<div>\u0000 \u0000 <p>Roselle extract (RE) is rich in anthocyanins and chlorogenic acids. This study investigated the health-promoting effects of RE on lipid metabolism, oxidative stress, glycometabolism, and gut microbiota in obese mice fed a high-fat diet (HFD). The obesity model was induced by feeding mice a HFD, with RE supplementation added to their drinking water at concentrations of 2 and 4 mg/mL for 12 weeks. RE significantly reduced body weight gain and fat accumulation compared to the control group, alleviated hepatic steatosis, and improved insulin sensitivity. Additionally, RE restored antioxidative enzyme activities such as SOD and GSH-PX while reducing MDA levels. Transcriptomic analysis of the liver was performed to evaluate gene expression related to lipid metabolism, particularly in the PPAR signaling pathway. Gut microbiota analysis showed that RE increased beneficial bacteria and reduced the <i>Firmicutes</i>-to-<i>Bacteroidetes</i> ratio, suggesting an improvement in gut dysbiosis caused by the HFD. RE enhanced lipid metabolism, reduced oxidative stress, and improved insulin sensitivity in obese mice, potentially through modulation of the PPAR signaling pathway and gut microbiota, suggesting its potential as a therapeutic candidate for obesity-related metabolic disorders.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gang Li, Ying Zhang, Yu Cheng, Hong Chao, Xiaolei Yang, Yan-Mei Dong, Xingsan Li, Haifeng Xue, Mingxia Wang, Lei Qi, Jicheng Liu
{"title":"Metabolomics Reveal the Anti-Hyperuricemia Effects and Mechanisms of Sunflower Head Extract in Hyperuricemia Mice Model","authors":"Gang Li, Ying Zhang, Yu Cheng, Hong Chao, Xiaolei Yang, Yan-Mei Dong, Xingsan Li, Haifeng Xue, Mingxia Wang, Lei Qi, Jicheng Liu","doi":"10.1002/mnfr.202401017","DOIUrl":"10.1002/mnfr.202401017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Hyperuricemia (HUA) is a globally prevalent metabolic disease characterized by excessive production or insufficient excretion of uric acid in the serum. Although several drugs are available for the treatment of HUA, they have been associated with undesirable side effects. Therefore, this study aims to evaluate the therapeutic effects of sunflower head extract (KHE) on HUA in a mouse model and explore its potential mechanisms. All mice were randomly divided into three groups: Normal control (NC, 0.5% CMC-Na), HUA model (MD, yeast extract paste 20 g/kg), and KHE treatment group (KHE, 1 g/kg). Biochemical indicators, the oxidative stress state, and metabolomics were analyzed. KHE reduced the levels of 5-aminoimidazole ribonucleotide, xanthine, hypoxanthine, and uric acid in the serum of mice with HUA but increased the levels of adenine and taurine. KHE decreased the activities of superoxide dismutase (SOD) enzymes, the hepatic hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and malondialdehyde (MDA) levels, and the serum levels of betaine aldehyde and beta-D-glucosamine. KHE improved oxidative stress levels and mitigated potential damage to the kidneys and joints caused by urate deposition. These findings provide comprehensive evidence supporting the anti-HUA effects and underlying mechanisms of KHE in HUA mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ashitaba Chalcone 4-Hydroxydericcin Promotes Glucagon-Like Peptide-1 Secretion and Prevents Postprandial Hyperglycemia in Mice","authors":"Kevin Odongo, Moe Ishinaka, Ayane Abe, Naoki Harada, Ryoichi Yamaji, Yoko Yamashita, Hitoshi Ashida","doi":"10.1002/mnfr.202400690","DOIUrl":"10.1002/mnfr.202400690","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Certain polyphenols improve glucose tolerance by stimulating glucagon-like peptide-1 (GLP-1) secretion from intestinal L-cells. Ashitaba chalcones, 4-hydroxyderricin (4-HD), and xanthoangelol (XAG) have antihyperglycemic effects, but their molecular mechanism, including whether they promote GLP-1 secretion is unknown. This study investigates the 4-HD-induced GLP-1 secretory mechanisms and its anti-hyperglycemic effects. The secretory mechanisms were examined in STC-1 cells and antihyperglycemic effects in male ICR mice. In STC-1 cells, 4-HD, but not XAG, stimulated GLP-1 secretion through membrane depolarization and intracellular Ca<sup>2+</sup> increase [Ca<sup>2+</sup>]<sub>i</sub>, via the L-type Ca<sup>2+</sup> channel (VGCC). Verapamil and nifedipine, blockers of VGCC, and treatment in Ca<sup>2+</sup>-free buffer abolished 4-HD effects on [Ca<sup>2+</sup>]<sub>i</sub> and GLP-1 secretion. Moreover, 4-HD activated CaMKII and ERK1/2. Consistently, oral 4-HD suppressed postprandial hyperglycemia in mice and increased plasma GLP-1 and insulin levels, GLUT4 translocation, and activation of LKB-1 and Akt pathways in skeletal muscle. Furthermore, exendin 9–39, a GLP-1R antagonist, and compound C, an AMPK inhibitor, completely canceled the 4-HD-caused anti-hyperglycemic activities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>4-HD stimulated GLP-1 secretion through membrane depolarization coupled with [Ca<sup>2+</sup>]<sub>i</sub> increase via VGCC in L-cells and activated AMPK- and insulin-induced GLUT4 translocation in skeletal muscle. Thus, 4-HD possesses dual mechanisms for the prevention of hyperglycemia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Novel Polysaccharide From Tremella fuciformis Alleviated High-Fat Diet-Induced Obesity by Promoting AMPK/PINK1/PRKN-Mediated Mitophagy in Mice","authors":"Jing Lu, Yanhui Zhang, Haizhao Song, Fang Wang, Luanfeng Wang, Ling Xiong, Xinchun Shen","doi":"10.1002/mnfr.202400699","DOIUrl":"10.1002/mnfr.202400699","url":null,"abstract":"<div>\u0000 \u0000 <p>Scope: Polysaccharides from <i>Tremella fuciformis</i> have gained significant interest due to their diverse biological activities. This study focuses on characterizing a purified polysaccharide, TPSP2, extracted from <i>T. fuciformis</i> and evaluating its antiobesity effect and underlying mechanisms in vivo. Methods and results: Structural analysis revealed that TPSP2, with a molecular weight of 1.51 × 10<sup>3</sup> kDa, is composed of mannose, rhamnose, glucuronic acid, galactose, xylose, arabinose, and fucose in specific molar ratios. The primary linkages identified include t-Fuc(p), 1,2-Xyl(p), t-GlcA(p), 1,3-Man(p), and 1,2,3-Man(p), with their corresponding ratios being 12.987%, 11.404%, 16.050%, 16.527%, and 26.624%, respectively. In vivo experiments demonstrated that TPSP2 significantly alleviated high-fat diet-induced weight gain, hyperlipidemia, hepatic steatosis, hyperglycemia, and insulin resistance in mice. Mechanistically, TPSP2 was found to enhance AMPK/PINK1-PRKN-dependent mitophagy by upregulating the p-AMPK/AMPK ratio, LC3-II/I ratio, and expression of PINK1, PRKN, prohibitin 2 (PHB2), and LAMP2, while downregulating p62 and TOM20 expression. Conclusion: This study suggested that TPSP2 could be a promising candidate for addressing obesity-related metabolic disorders by targeting mitochondrial quality control mechanisms.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francis Foata, Stéphane Duboux, Sébastien Herzig, Federico Sizzano, Jonathan Thevenet, Philippe Guy, Serge Rezzi, Sylviane Métairon, Bertrand Bourqui, Ivan Montoliu, Annick Mercenier, Nabil Bosco
{"title":"Identification and Biological Characterization of a Novel NRF2 Activator Molecule Released From the Membranes of Heat-Treated Bifidobacterium breve NCC 2950","authors":"Francis Foata, Stéphane Duboux, Sébastien Herzig, Federico Sizzano, Jonathan Thevenet, Philippe Guy, Serge Rezzi, Sylviane Métairon, Bertrand Bourqui, Ivan Montoliu, Annick Mercenier, Nabil Bosco","doi":"10.1002/mnfr.202400770","DOIUrl":"https://doi.org/10.1002/mnfr.202400770","url":null,"abstract":"Postbiotics are defined as a “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”. They represent an attractive alternative to probiotics as they could be used in a broader range of applications, where probiotic stability is limiting. To date knowledge on the mechanism of action of inanimate microorganisms is relatively scarce. In this study, we investigated the impact of heat treatment on NRF2 activation by several candidate probiotic strains from the Nestlé Culture Collection (NCC), including species encompassed in the <i>Bifidobacterium</i> genus and the <i>Lactobacillaceae</i> family. We identified an NRF2-activating bioactive molecule, 4-oxo-2-pentenoic acid (OPA), specifically released during heat treatment of <i>Bifidobacterium breve</i> NCC 2950. We explored cellular pathways that can be modulated by OPA, such as antiinflammatory signals and organismal defense against oxidative stress in zebrafish in vivo. We identified a new <i>B. breve</i> NCC 2950-derived postbiotic that, based on the mode of action, may have important applications for nutritional strategies to benefit human health.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"64 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fishing for Solutions: How Pre-Conceptional Fish Oil Supplementation in Obese Fathers Reduces Risk of Non-Alcoholic Fatty Liver Disease in Offspring Mice","authors":"Junhui Yang, Akriti Shrestha, Latha Ramalingam","doi":"10.1002/mnfr.202400452","DOIUrl":"10.1002/mnfr.202400452","url":null,"abstract":"<p>Metabolic dysfunction associated fatty liver disease (MAFLD) is a chronic condition with hepatic fat accumulation. The intergenerational effect of obesity has predominantly focused on mothers, with limited studies on paternal obesity. Nutritional intervention with fish oil (FO) has beneficial effects in reducing markers of obesity. We hypothesized that supplementing obese fathers with FO before conception could enhance the metabolic health of their offspring liver. Male mice were assigned to low-fat (LF), high fat (HF), or HF supplemented with FO for 10 weeks. Subsequently, these males were mated with females on a chow diet. Offspring were sacrificed at 8 weeks, and liver tissues were analyzed for gene expression and histology. Offspring body weight was not significantly impacted by paternal diet. However, male offspring of HF fathers had higher levels of markers of inflammation and fatty acid synthesis compared to offspring of LF fed fathers. Paternal FO supplementation significantly reduced fatty acid synthesis and glucose metabolism, while increasing fatty acid oxidation in male offspring, with a less pronounced effect in female offspring. These findings suggest that FO supplementation in obese fathers prior to conception attenuates the development of MAFLD in male offspring. This data underscores the significance of paternal nutritional intervention in promoting offspring health.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.202400452","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janina Weigant, Anuschka Afchar, Meike Barzen, Lisa Dicks, Benno F. Zimmermann, Matthias Schmid, Leonie Weinhold, Birgit Stoffel-Wagner, Jörg Ellinger, Peter Stehle, Sabine Ellinger
{"title":"Cardiometabolic Impact of Encapsulated Cocoa Powder and Pure Cocoa Ingredients Supplementation: A Comparative Placebo-Controlled RCT in Adults","authors":"Janina Weigant, Anuschka Afchar, Meike Barzen, Lisa Dicks, Benno F. Zimmermann, Matthias Schmid, Leonie Weinhold, Birgit Stoffel-Wagner, Jörg Ellinger, Peter Stehle, Sabine Ellinger","doi":"10.1002/mnfr.202400490","DOIUrl":"10.1002/mnfr.202400490","url":null,"abstract":"<p>Consuming cocoa rich in flavan-3-ols (particularly epicatechin [EC]) may reduce vascular stiffness and blood pressure (BP) and improve serum lipid profiles. Because interventional studies on pure EC exhibited inconclusive results, the role of other cocoa ingredients such as methylxanthines (MX) on vascular health was assumed. This study aimed to systematically compare the effects of flavanol-rich cocoa and its major components EC and MX on vascular function and serum lipid levels. In a randomized controlled trial (RCT), 75 healthy young adults ingested capsules containing either (i) flavanol-rich cocoa powder, (ii) EC, (iii) MX, (iv) EC + MX, or (v) placebo (<i>n </i>= 15 per group) daily for 4 weeks. Capsules provided equal amounts of EC and/or MX as the cocoa capsules. Pulse wave velocity (PWV), BP, endothelin-1, and lipids were investigated before and after intervention. No group-specific statistically significant differences in aortic PWV (<i>p </i>= 0.410) or any other parameters (<i>p </i>≥ 0.05) were observed between before and after the intervention. Daily intake of neither flavanol-rich cocoa nor pure cocoa ingredients influenced vascular function and lipid profiles in healthy adults. Consequently, RCTs involving subjects with increased cardiometabolic risk may clarify the effects of EC and MX as cocoa components on cardiovascular health parameters.</p><p><b>Trial Registration</b>: URL: https://drks.de/search/en/trial. Unique identifier: DRKS00022056</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.202400490","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143084167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel Combination of Traditional Ayurvedic Herb Piper longum L. and Modern Stem Cell Therapy for the Reversal of Glucocorticoid-Induced Osteoporosis","authors":"Avinash Sanap, Ramesh Bhonde, Madhura Shekatkar, Avinash Kharat, Supriya Kheur, Vaishali Undale, Nilima Dharkar, Girish Tillu, Kalpana Joshi","doi":"10.1002/mnfr.202400698","DOIUrl":"10.1002/mnfr.202400698","url":null,"abstract":"<div>\u0000 \u0000 <p>Glucocorticoids induced osteoporosis (GIOP) is a global concern without effective therapies. The present study investigated the potential of the umbilical cord-derived mesenchymal stem cells (UCMSCs) and traditional medicine <i>Piper longum</i> L. in the reversal of GIOP. Twelve-week-old female Swiss Albino mice were subjected to the dexamethasone treatment for 4 weeks to induce GIOP. Further, the mice were randomized into four different groups for treatment, viz., phosphate buffered saline (PBS), UCMSCs, <i>P. longum</i> L. aqueous extract through feed, and a combination of UCMSCs and <i>P. longum</i> L. extract. Post therapy, GIOP mice regained the weight and hair loss in the UCMSCs and <i>P. longum</i> L. extract group. ALP activity and mRNA expression of RunX2, ALP, and OPN were significantly increased. Micro-CT analysis revealed remarkable improvement in key parameters such as bone volume, bone surface density, tissue surface, trabecular thickness, and number. Our results unequivocally demonstrate that a combination of the UCMSCs and <i>P. longum</i> L. is highly effective in the reversal of GIOP as compared to <i>P. longum</i> L. or UCMSCs alone. The therapeutic effect can be attributed to the osteogenic and paracrine potential of UCMSCs and the anti-inflammatory effect of <i>P. longum</i> L.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"69 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}