Anqi Zhao, Jiaxuan Li, Mark Peterson, Molly Black, Christopher A. Gaulke, Elizabeth H. Jeffery, Michael J. Miller
Brassica vegetables contain unique compounds known as glucosinolates (GSLs), which, when hydrolyzed by plant or microbial myrosinase, form bioactive isothiocyanates (ITCs) that offer health benefits to the host. The present study evaluated the impact of cooked broccoli (broccoli myrosinase inactivated) consumption on cecal microbial metabolism of glucoraphanin (GRP) in lean and obese mice and characterized the changes in cecal microbiota following broccoli-containing diets.
{"title":"Cooked Broccoli Alters Cecal Microbiota and Impacts Microbial Metabolism of Glucoraphanin in Lean and Obese Mice","authors":"Anqi Zhao, Jiaxuan Li, Mark Peterson, Molly Black, Christopher A. Gaulke, Elizabeth H. Jeffery, Michael J. Miller","doi":"10.1002/mnfr.202400813","DOIUrl":"https://doi.org/10.1002/mnfr.202400813","url":null,"abstract":"Brassica vegetables contain unique compounds known as glucosinolates (GSLs), which, when hydrolyzed by plant or microbial myrosinase, form bioactive isothiocyanates (ITCs) that offer health benefits to the host. The present study evaluated the impact of cooked broccoli (broccoli myrosinase inactivated) consumption on cecal microbial metabolism of glucoraphanin (GRP) in lean and obese mice and characterized the changes in cecal microbiota following broccoli-containing diets.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435627","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}
Érique Castro, Thayna S. Vieira, Álbert S. Peixoto, Bianca F. Leonardi, Caroline A. Tomazelli, Caroline A. Lino, Tiago E. Oliveira, Natália M. Pessoa, Erika V. M. Pessoa, Marina A. Abe‐Honda, Natália Pontara‐Corte, Luciano P. Silva‐Junior, Ana B. Pires, Adriano B. Chaves‐Filho, Naima Moustaid‐Moussa, William T. Festuccia
Fish oil rich in omega‐3 polyunsaturated fatty acids (n‐3 PUFAs) improves rodent glucose homeostasis and insulin sensitivity through unknown mechanisms. We investigated the involvement of adipocyte Rictor/mTORC2 as a mediator of fish oil and n‐3 PUFA eicosapentaenoic acid (EPA) effects. Male mice bearing or not Rictor/mTORC2 deficiency in adipocytes were fed isocaloric high fat diets produced either with lard (HFD) or fish oil (HFn3) and evaluated for glucose homeostasis and insulin sensitivity. HFn3 intake improved glucose tolerance and insulin sensitivity, increased glucose uptake in adipose tissue and skeletal muscle per unit of insulin, and reduced hepatic glucose production as well as adipose tissue and liver de novo fatty acid synthesis. Interestingly, this improvement in glucose homeostasis was concurrent with low serum insulin levels and increased content of Ser473 phosphorylated (p) Akt in adipose tissue, but not skeletal muscle and liver. Intake of an HFD supplemented with EPA increased, in an mTORC2‐dependent manner, insulin sensitivity and adipocyte pAkt Ser473, but not glucose tolerance. In conclusion, adipocyte mTORC2 mediates in part the improvement in insulin sensitivity induced by fish oil and EPA, while the improvement in glucose tolerance induced by fish oil seems to be triggered by mTORC2‐independent actions in muscle and liver.
{"title":"Fish Oil and EPA Improve Insulin Sensitivity, in Part Through Adipocyte mTORC2 Activation in Diet‐Induced Obese Male Mice","authors":"Érique Castro, Thayna S. Vieira, Álbert S. Peixoto, Bianca F. Leonardi, Caroline A. Tomazelli, Caroline A. Lino, Tiago E. Oliveira, Natália M. Pessoa, Erika V. M. Pessoa, Marina A. Abe‐Honda, Natália Pontara‐Corte, Luciano P. Silva‐Junior, Ana B. Pires, Adriano B. Chaves‐Filho, Naima Moustaid‐Moussa, William T. Festuccia","doi":"10.1002/mnfr.70001","DOIUrl":"https://doi.org/10.1002/mnfr.70001","url":null,"abstract":"Fish oil rich in omega‐3 polyunsaturated fatty acids (<jats:italic>n</jats:italic>‐3 PUFAs) improves rodent glucose homeostasis and insulin sensitivity through unknown mechanisms. We investigated the involvement of adipocyte Rictor/mTORC2 as a mediator of fish oil and <jats:italic>n</jats:italic>‐3 PUFA eicosapentaenoic acid (EPA) effects. Male mice bearing or not Rictor/mTORC2 deficiency in adipocytes were fed isocaloric high fat diets produced either with lard (HFD) or fish oil (HFn3) and evaluated for glucose homeostasis and insulin sensitivity. HFn3 intake improved glucose tolerance and insulin sensitivity, increased glucose uptake in adipose tissue and skeletal muscle per unit of insulin, and reduced hepatic glucose production as well as adipose tissue and liver de novo fatty acid synthesis. Interestingly, this improvement in glucose homeostasis was concurrent with low serum insulin levels and increased content of Ser473 phosphorylated (p) Akt in adipose tissue, but not skeletal muscle and liver. Intake of an HFD supplemented with EPA increased, in an mTORC2‐dependent manner, insulin sensitivity and adipocyte pAkt Ser473, but not glucose tolerance. In conclusion, adipocyte mTORC2 mediates in part the improvement in insulin sensitivity induced by fish oil and EPA, while the improvement in glucose tolerance induced by fish oil seems to be triggered by mTORC2‐independent actions in muscle and liver.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"80 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435299","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}
Agaricus blazei Murill polysaccharide (ABMP) has been found to exhibit significant immune regulatory effects, making them a promising candidate for complementary to the pharmacological treatment of colorectal cancer immune-related diseases. As the prevalence of colorectal cancer among younger individuals increases, the possible age-dependent anticancer modulatory effect of ABMP has not been clarified. This study evaluated the age-dependent immunoregulatory efficacy of polysaccharides extraction from A. blazei in colon tumor. Hematoxylin-eosin staining, immunohistochemistry, and vibrational spectroscopic image analysis of subcutaneous tumor tissues after ABMP preventive intervention for 14 weeks were analyzed in depth. In vivo data demonstrated that ABMP could more effectively inhibit the growth of tumor in mice at 8 compared with 12 months old without toxic side effect. Concurrently, Raman imaging spectroscopy analysis showed that ABMP preventive intervention could significantly reduce the lipid content in the tumor microenvironment (TME) of 8-month-old subcutaneous tumor-bearing mice, suggesting that the changes in lipid content in TME are closely related to anticancer activity. These results stress the importance of considering age as a factor in polysaccharide adjuvant anticancer therapy. This work highlights for the first time that age is a key determinant in the ABMP preventive effectiveness by affecting lipid levels in the TME of tumor-bearing mice, thereby exerting anticancer activity.
{"title":"The Age-Dependent Anticancer Efficacy of Agaricus blazei Murill Polysaccharide in Colon Cancer.","authors":"Yongzhao Xu, Tianxiong Xu, Chujun Huang, William Kwame Amakye, Kaiqiang Li, Ying Zhu, Jiaoyan Ren","doi":"10.1002/mnfr.202400733","DOIUrl":"https://doi.org/10.1002/mnfr.202400733","url":null,"abstract":"<p><p>Agaricus blazei Murill polysaccharide (ABMP) has been found to exhibit significant immune regulatory effects, making them a promising candidate for complementary to the pharmacological treatment of colorectal cancer immune-related diseases. As the prevalence of colorectal cancer among younger individuals increases, the possible age-dependent anticancer modulatory effect of ABMP has not been clarified. This study evaluated the age-dependent immunoregulatory efficacy of polysaccharides extraction from A. blazei in colon tumor. Hematoxylin-eosin staining, immunohistochemistry, and vibrational spectroscopic image analysis of subcutaneous tumor tissues after ABMP preventive intervention for 14 weeks were analyzed in depth. In vivo data demonstrated that ABMP could more effectively inhibit the growth of tumor in mice at 8 compared with 12 months old without toxic side effect. Concurrently, Raman imaging spectroscopy analysis showed that ABMP preventive intervention could significantly reduce the lipid content in the tumor microenvironment (TME) of 8-month-old subcutaneous tumor-bearing mice, suggesting that the changes in lipid content in TME are closely related to anticancer activity. These results stress the importance of considering age as a factor in polysaccharide adjuvant anticancer therapy. This work highlights for the first time that age is a key determinant in the ABMP preventive effectiveness by affecting lipid levels in the TME of tumor-bearing mice, thereby exerting anticancer activity.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":" ","pages":"e202400733"},"PeriodicalIF":4.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412621","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}
Adipose tissue dysfunction due to insulin resistance (IR) plays a central role in the development of metabolic diseases. Obesity-associated IR greatly attributes to low-grade inflammation and high circulating levels of FFAs and sugar. 3T3-L1 adipocytes exposed to a mixture of TNF-α, fructose, and palmitate acid for 24 h were validated as a model to simulate the pathogenesis of IR in obese people under a high–fat–fructose diet. Results show that the combined induction medium (CIM) successfully induced IR in 3T3-L1 adipocytes by impairing insulin signaling pathway. In the meantime, MAPK (JNK, ERK) pathway and NFκB p65 were activated, which are signs of inflammation response. Moreover, CIM caused mitochondrial dysfunction and oxidative stress. In addition, endoplasmic reticulum stress (ER stress) was evoked by CIM through activating IRE1α/XBP1s, eIF2α, and ATF6. Apigenin could efficiently relieve IR in adipocytes through sensitizing insulin signaling pathway, exerting antioxidant activity, blocking the NFκB pathway, and suppressing ER stress. The present study may provide new tools in discovering preventive and intervention strategies for IR caused by low-grade inflammation and high–fat–fructose diets and provide a basis for the application of apigenin in IR and other IR-related diseases.
{"title":"Apigenin Ameliorates Insulin Resistance in 3T3-L1 Adipocytes: Establishment of a New Insulin Resistance Model Induced by Combined Treatments","authors":"Xiaoxuan Guo, Bing Xia, Sha Liu, Ying Dong, Yongzhong Qian, Jing Qiu","doi":"10.1002/mnfr.202400545","DOIUrl":"https://doi.org/10.1002/mnfr.202400545","url":null,"abstract":"Adipose tissue dysfunction due to insulin resistance (IR) plays a central role in the development of metabolic diseases. Obesity-associated IR greatly attributes to low-grade inflammation and high circulating levels of FFAs and sugar. 3T3-L1 adipocytes exposed to a mixture of TNF-α, fructose, and palmitate acid for 24 h were validated as a model to simulate the pathogenesis of IR in obese people under a high–fat–fructose diet. Results show that the combined induction medium (CIM) successfully induced IR in 3T3-L1 adipocytes by impairing insulin signaling pathway. In the meantime, MAPK (JNK, ERK) pathway and NFκB p65 were activated, which are signs of inflammation response. Moreover, CIM caused mitochondrial dysfunction and oxidative stress. In addition, endoplasmic reticulum stress (ER stress) was evoked by CIM through activating IRE1α/XBP1s, eIF2α, and ATF6. Apigenin could efficiently relieve IR in adipocytes through sensitizing insulin signaling pathway, exerting antioxidant activity, blocking the NFκB pathway, and suppressing ER stress. The present study may provide new tools in discovering preventive and intervention strategies for IR caused by low-grade inflammation and high–fat–fructose diets and provide a basis for the application of apigenin in IR and other IR-related diseases.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"130 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401492","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}
Kun Xie, Satoshi Yano, Jinyun Wang, Shota Yamakoshi, Tomoe Ohta, Takuhiro Uto, Maiko Sakai, Xi He, Kaichi Yoshizaki, Takumi Kubota, Kohta Ohnishi, Taichi Hara
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 EGR1 was the most significantly altered gene in YF-treated OUMS-36T-1 cells. YF-treated EGR1-deficient HAP1 cells displayed reduced autophagic flux (p < 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 (p > 0.05); however, treatment with SPD and SPM in the same ratio as that found in YF increased autophagic flux (p < 0.05). This specific SPM/SPD ratio reduced MG132-induced proteostress via EGR1-dependent pathways (p < 0.05). Thus, the SPM/SPD balance may regulate autophagy via EGR1-dependent pathways, and controlling this balance may provide a strategy to maintain cellular homeostasis.
{"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":"https://doi.org/10.1002/mnfr.202400606","url":null,"abstract":"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.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"161 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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
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 Firmicutes-to-Bacteroidetes 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.
{"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":"https://doi.org/10.1002/mnfr.202400756","url":null,"abstract":"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.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"6 1","pages":""},"PeriodicalIF":5.2,"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
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 (H2O2) 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.
{"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":"https://doi.org/10.1002/mnfr.202401017","url":null,"abstract":"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.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"12 1","pages":""},"PeriodicalIF":5.2,"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}
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 Ca2+ increase [Ca2+]i, via the L-type Ca2+ channel (VGCC). Verapamil and nifedipine, blockers of VGCC, and treatment in Ca2+-free buffer abolished 4-HD effects on [Ca2+]i 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.
{"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":"https://doi.org/10.1002/mnfr.202400690","url":null,"abstract":"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.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"3 1","pages":""},"PeriodicalIF":5.2,"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}
Scope: Polysaccharides from Tremella fuciformis have gained significant interest due to their diverse biological activities. This study focuses on characterizing a purified polysaccharide, TPSP2, extracted from T. fuciformis 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 × 103 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.
{"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":"https://doi.org/10.1002/mnfr.202400699","url":null,"abstract":"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.","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"85 5 1","pages":""},"PeriodicalIF":5.2,"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
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 Bifidobacterium genus and the Lactobacillaceae family. We identified an NRF2-activating bioactive molecule, 4-oxo-2-pentenoic acid (OPA), specifically released during heat treatment of Bifidobacterium breve 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 B. breve NCC 2950-derived postbiotic that, based on the mode of action, may have important applications for nutritional strategies to benefit human health.
{"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}
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