{"title":"Changes in lipid metabolism in the visceral rather than the subcutaneous adipose tissue depot attenuate metabolic disturbances in obesity-resistant mice fed a high-fat diet","authors":"Miloš Vratarić , Ana Teofilović , Danijela Vojnović Milutinović , Nataša Veličković , Ljubica Vučićević , Goran Đmura , Ana Djordjevic","doi":"10.1016/j.jnutbio.2025.109912","DOIUrl":"10.1016/j.jnutbio.2025.109912","url":null,"abstract":"<div><div>Obesity is characterized by an enlargement of white adipose tissue caused by caloric excess. The depot-specific adaptation of white adipose tissue in individuals resistant to obesity despite a high-calorie diet is crucial for understanding the pathogenesis of obesity and related metabolic disorders. Our aim was to characterize the metabolic and morphological state of obesity resistance and to investigate depot-specific changes in signaling pathways in epididymal visceral (eVAT) and inguinal subcutaneous (iSAT) white adipose tissue of C57BL/6J male mice on a high-fat diet (60 kcal% fats). After 14 weeks, the mice were categorized as obese (at least 30% higher body mass compared to the control group) or obesity-resistant (weight gain below 30%). Biochemical and morphological parameters, as well as histology, and signaling pathways involved in lipid metabolism, inflammation, and insulin sensitivity were investigated in eVAT and iSAT. The results showed unaltered body, total VAT and iSAT mass in obesity-resistant mice despite increased caloric intake. Leptin levels and glucose homeostasis were improved in these animals compared to the obese mice. In both eVAT and iSAT of the obesity-resistant mice, adipocyte size and lipolytic capacity were retained at control levels, while compared to the obese mice, preserved capacity for adipogenesis, improved local insulin sensitivity and the absence of inflammation were observed only in the eVAT. In conclusion, metabolic adaptation of eVAT rather than iSAT may have a substantial impact on the maintenance of the obesity-resistant phenotype with fewer metabolic complications, which could contribute to the improvement of existing obesity therapies.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109912"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniëlle D.B. Holthuijsen , Eline H. van Roekel , Martijn J.L. Bours , Per M. Ueland , Stéphanie O. Breukink , Maryska L.G. Janssen-Heijnen , Joop L. Konsten , Eric T.P. Keulen , Adrian McCann , Stefanie Brezina , Biljana Gigic , Dieuwertje E. Kok , Cornelia M. Ulrich , Matty P. Weijenberg , Simone J.P.M. Eussen
{"title":"Modeling how iso-caloric macronutrient substitutions are longitudinally associated with plasma kynurenines in colorectal cancer survivors up to 12 months post-treatment","authors":"Daniëlle D.B. Holthuijsen , Eline H. van Roekel , Martijn J.L. Bours , Per M. Ueland , Stéphanie O. Breukink , Maryska L.G. Janssen-Heijnen , Joop L. Konsten , Eric T.P. Keulen , Adrian McCann , Stefanie Brezina , Biljana Gigic , Dieuwertje E. Kok , Cornelia M. Ulrich , Matty P. Weijenberg , Simone J.P.M. Eussen","doi":"10.1016/j.jnutbio.2025.109910","DOIUrl":"10.1016/j.jnutbio.2025.109910","url":null,"abstract":"<div><div>Dietary intake of several macronutrients is associated with plasma kynurenines after colorectal cancer (CRC), and kynurenines have been linked to health-related outcomes. It is unknown how macronutrient substitution affects plasma kynurenines, which may be relevant for developing guidelines to improve post-CRC quality of life through dietary changes. Using iso-caloric substitution models, we investigated how substituting one macronutrient with another is longitudinally associated with plasma tryptophan, kynurenines, and kynurenine ratios in CRC survivors. Measurements were performed at 6-weeks, 6-months, and 12-months post-treatment in 247 stage I–III CRC survivors. Macronutrient intake was measured by 7-d dietary records and plasma kynurenines by LC/MS-MS. For analysis, we applied linear mixed models with false discovery rate (FDR) to adjust for multiple testing. After FDR adjustment, substituting 100 kcal/d of total carbohydrates with 100 kcal/d of total protein was associated with higher plasma concentrations of kynurenic acid (KA), xanthurenic acid (XA), and a higher kynurenic acid-to-quinolinic acid (KA/QA) ratio. Substituting 100 kcal/d of total carbohydrates with 100 kcal/d of total fat was associated with higher tryptophan concentrations, higher KA/QA ratio, and a lower kynurenine-to-tryptophan ratio (KTR) and hydroxykynurenine ratio (HKr). Substituting 100 kcal/d of total fat with 100 kcal/d of total protein was associated with higher XA concentrations. Altogether, iso-caloric macronutrient substitutions, particularly substituting carbohydrates with protein or fat, were longitudinally associated with higher concentrations of potentially favourable kynurenines and ratios (i.e., KA, XA, and KA/QA ratio) and lower ratios with pro-inflammatory or neurotoxic properties (i.e., KTR and HKr) in CRC survivors up to 12-months post-treatment.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109910"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaxiang Zhu , Bingke Wang , Jianshuang Ma , Changchang Pu , Lu Wang , Feng Yang , Yong Deng , Chunnuan Zhang
{"title":"Sulforaphanin ameliorates the damage of the Cyprinus carpio liver induced by Aeromonas hydrophila via activating AMPK pathway","authors":"Jiaxiang Zhu , Bingke Wang , Jianshuang Ma , Changchang Pu , Lu Wang , Feng Yang , Yong Deng , Chunnuan Zhang","doi":"10.1016/j.jnutbio.2025.109911","DOIUrl":"10.1016/j.jnutbio.2025.109911","url":null,"abstract":"<div><div>This study aims to explore how the sulforaphane (SFN) exerts a mitigating effect on the liver injury of <em>Cyprinus carpio</em> (<em>C. carpio</em>) caused by <em>Aeromonas hydrophila</em> (<em>A. hydrophila</em>). A total of 450 <em>C. carpio</em>. (40.2 ± 2.8 g) were randomly assigned to five groups, each consisting of three replicates. The control group was not infected with <em>A. hydrophila</em> and was fed with the ordinary commercial feed. The other different groups were attacked by <em>A. hydrophila</em> and fed four sulforaphane-graded diets (0, 10, 15, and 20 mg/kg) for 8 weeks. The findings indicated that supplementation SFN (15 and 20 mg/kg) could recover or even significantly reduce the levels of tumor necrosis factor-α (TNF-α) ,interleukin-1β (IL-1β) and IL-6 and increased the level of IL-10 in the liver by repressing the NF-κB signaling pathway compared to the only <em>A. hydrophila</em>-infection group (<em>P</em> < .05). Also, SFN supplementation increased the immunoglobulin M (IgM) level, complement 3 (C3) and C4 concentrations in comparison with the only <em>A. hydrophila</em>-infection group in the liver of <em>C. carpio</em> to enhance the immune function (<em>P</em> < .05). After that, transcriptome through KEGG enrichment analysis suggested that differentially expressed genes (DEGs) were associated with immunological diseases, as well as fat digestion and absorption pathways. Notably, these pathways include antigen processing and presentation, as well as the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR) signaling pathways. In conclusion, it was determined that <em>C. carpio</em> fed with suitable amount (15 mg/kg) of SFN improved lipid deposition caused by <em>A. hydrophila</em> via regulating the lipid metabolism pathway.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109911"},"PeriodicalIF":4.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiuchuan Hu , Rui Wang , Peter Kille , Wolfgang Maret , Christer Hogstrand
{"title":"Zinc amino acid chelate and the Aryl Hydrocarbon Receptor (AHR) cooperate in improving the barrier function of a Caco-2 cell intestinal epithelium","authors":"Xiuchuan Hu , Rui Wang , Peter Kille , Wolfgang Maret , Christer Hogstrand","doi":"10.1016/j.jnutbio.2025.109909","DOIUrl":"10.1016/j.jnutbio.2025.109909","url":null,"abstract":"<div><div>Zinc and several physiologically relevant ligands of the aryl hydrocarbon receptor (AHR) are nutrients that promote intestinal barrier function. We have identified that AHR activation upregulates the expression of zinc importers in the intestinal epithelium to increase intracellular zinc concentrations, which leads to improved epithelial barrier function. Here, we investigated if an amino acid chelate of zinc, in cooperation with AHR activation, can improve the barrier function of a differentiated Caco-2 cell epithelium. Functional assays of the Caco-2 cell epithelium demonstrate that both ZnSO<sub>4</sub> and a lysine and glutamic acid chelate of Zn, in combination with the physiological AHR agonist 6-formylindolo[3,2-b]carbazole (FICZ), increase expression of tight junction proteins at the mRNA and protein levels. FICZ increases uptake of zinc into the epithelium in the presence of ZnSO<sub>4</sub> or the amino acid Zn chelate in the medium to equal extents. We conclude that the lysine and glutamic acid chelate of Zn is as efficacious as ZnSO<sub>4</sub> in reducing permeability of the Caco-2 cell epithelium in the presence of FICZ. The results suggest that dietary supplementation with bioavailable forms of zinc together with nutritional AHR agonists may be beneficial in improving gut barrier function and help prevent inflammatory bowel disease (IBD).</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109909"},"PeriodicalIF":4.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chi Wang , Xiaotian Zhang , Guohao Liu , Cheng Zhang, Pengju Li, Pan He, Sha Liu, Hong Ji, Haibo Yu
{"title":"Selenium alleviates high-fat diet induced hepatocyte lipid accumulation via exosome miR-22/FGFR1 pathway in grass carp","authors":"Chi Wang , Xiaotian Zhang , Guohao Liu , Cheng Zhang, Pengju Li, Pan He, Sha Liu, Hong Ji, Haibo Yu","doi":"10.1016/j.jnutbio.2025.109907","DOIUrl":"10.1016/j.jnutbio.2025.109907","url":null,"abstract":"<div><div>The current study aims to investigate whether exosomal miRNAs are involved in lipid reduction by selenium (Se) in the liver of grass carp, through miRNA sequencing, transfection of miRNA mimic (miR-22m) or inhibitor (miR-22i), isolation of hepatocyte-derived exosomes and treatment, and detection of lipid metabolism-related genes and proteins. The miRNAs sequencing and bioinformatics revealed that miR-22 was most abundantly expressed in the differentially expressed miRNAs after selenium treatment, and was enriched in lipid metabolism-related pathways. Moreover, Se significantly up-regulated the miR-22 levels and reduced the lipid content in liver or hepatocytes of grass carp. Furthermore, the miR-22m significantly increased levels of miR-22 and reduced lipid content in grass carp hepatocytes, which were consistent with the Se-treatment. However, the miR-22i reversed these trends. Besides, the miR-22 suppressed the FGFR1-PI3K-AKT-mTOR signaling pathway and its downstream genes related to lipid synthesis. More importantly, the Se-treated hepatocyte-exosomes which were enriched in the miR-22 significantly reduced the triglycerides content in the oleic acid-treated hepatocytes. In summary, Se alleviated high fat-induced lipid accumulation in grass carp liver by up-regulating the expression of miR-22 which negatively regulates FGFR1 and its downstream regulatory genes. Moreover, exosomes participate in the lipid reduction by Se, which may be through carrying miR-22.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109907"},"PeriodicalIF":4.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoqin Ding , Yan Chen , Lanlan Du , Jing Li , Xiuhua Meng , Han Lv , Bei Tong , Guanting Niu , Tunyu Jian , Jian Chen
{"title":"Benefits of inulin and fructo-oligosaccharides on high fat diet-induced type 2 diabetes mellitus by regulating the gut microbiota in mice","authors":"Xiaoqin Ding , Yan Chen , Lanlan Du , Jing Li , Xiuhua Meng , Han Lv , Bei Tong , Guanting Niu , Tunyu Jian , Jian Chen","doi":"10.1016/j.jnutbio.2025.109908","DOIUrl":"10.1016/j.jnutbio.2025.109908","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) is pathologically associated with gut microbiota imbalance, which is implicated in disease progression through metabolic and inflammatory pathways. The therapeutic potential of inulin, a well-characterized prebiotic, has been explored to mitigate T2DM via microbiota modulation. However, the efficacy of this intervention, with its performance dependent on the degree of polymerization (DP), requires further investigation. This study assessed the therapeutic roles of inulin (DP3-60) and fructo-oligosaccharides (FOS, DP3-10) in T2DM management. Dietary administration of these prebiotic compounds demonstrated a significant capacity to alleviate multiple metabolic pathologies, including obesity, insulin resistance, systemic inflammation, oxidative stress, dyslipidemia and hepatic steatosis in high-fat diet (HFD)-fed induced T2DM mice. Significant superior efficacy was observed in FOS for ameliorating glucose metabolic dysregulation, adipocyte hypertrophy, liver weight, and histopathological alterations in colonic tissue, while inulin exhibited greater potency in alleviating oxidative stress. Both inulin and FOS enhanced gut microbiota diversity and richness in T2DM mice, accompanied by a significant reduction in Firmicutes/Bacteroidetes ratio. Notably, the S24-7 family emerged as a crucial microbial taxon modulated by both inulin and FOS. Furthermore, FOS demonstrated superior capacity to restore HFD-induced gut microbiota. Taxonomically significant amplicon sequence variants (ASVs), which were altered by HFD and modulated by inulin and FOS, exhibited distinct taxonomic profiles between the two compounds. This study provides preliminary evidence that the biological effects and beneficial properties of inulin-type fructans exhibit DP-dependent variations, which may enhance their efficient utilization in metabolic disorders.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109908"},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuulia Onali , Hana Slabá , Ching Jian , Tuuli Koivumäki , Essi Päivärinta , Maija Marttinen , Maija Määttänen , Anne Salonen , Anne-Maria Pajari
{"title":"Berry supplementation in healthy volunteers modulates gut microbiota, increases fecal polyphenol metabolites and reduces viability of colon cancer cells exposed to fecal water- a randomized controlled trial","authors":"Tuulia Onali , Hana Slabá , Ching Jian , Tuuli Koivumäki , Essi Päivärinta , Maija Marttinen , Maija Määttänen , Anne Salonen , Anne-Maria Pajari","doi":"10.1016/j.jnutbio.2025.109906","DOIUrl":"10.1016/j.jnutbio.2025.109906","url":null,"abstract":"<div><div>Diets high in red and processed meat and low in plant-based foods are associated with an increased risk of colorectal cancer. We investigated whether berry supplementation can impact gut metabolism to counteract the presumably cancer promoting luminal environment sustained by high red and processed meat consumption. Altogether 43 healthy adults were randomized either into Meat group (150 g/d red and processed pork meat) or Meat & Berries group (150 g/d red and processed meat and 200 g/d of mixed berries). Fecal samples and 3-d food records were collected at baseline and at the end of the four-week intervention. Intakes of vitamin C, vitamin E, manganese, insoluble fiber<em>,</em> and the polyphenols available in the database were significantly higher in the Meat & Berries than Meat group. While between-group comparisons found no significant differences in the gut microbiota, the within-group analyses showed that the relative abundances of beneficial <em>Roseburia</em> and <em>Faecalibacterium</em> were decreased and an unclassified group of <em>Peptostreptococcaceae</em> increased significantly in the Meat group. In comparison to the Meat group, berry consumption resulted in higher fecal concentrations of <em>p</em>-coumaric and protocatechuic acids and lower viability of fecal water (FW) -treated CV1-P fibroblastoma and human colon adenocarcinoma HCA-7 and Caco-2 cells (<em>P<</em>.05 with 30% FW). Berry consumption provided protective nutrients and mitigated potentially unfavourable gut microbiota changes seen in the Meat group, increased fecal polyphenol metabolites, and reduced viability of FW-treated colon adenocarcinoma cells, collectively suggesting that berries may protect against colorectal cancer development.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109906"},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmad Ud Din , Michael G. Sweet , Ashley M. McAmis , Juanita G. Ratliff , Pon Velayutham Anandh Babu , Andrew P. Neilson
{"title":"Establishing reliable blood biomarkers for trimethylamine N-oxide status in rodents: Effects of oral choline challenge, dietary choline and fasting conditions","authors":"Ahmad Ud Din , Michael G. Sweet , Ashley M. McAmis , Juanita G. Ratliff , Pon Velayutham Anandh Babu , Andrew P. Neilson","doi":"10.1016/j.jnutbio.2025.109905","DOIUrl":"10.1016/j.jnutbio.2025.109905","url":null,"abstract":"<div><div>Circulating concentrations of the gut microbial-mammalian metabolite trimethylamine N-oxide (TMAO) are linked to atherosclerosis risk. TMAO biosynthesis begins when dietary choline is converted to trimethylamine (TMA) by gut microbial TMA lyase. TMA is transported to the liver, where flavin-containing monooxygenases convert it to TMAO. While dietary modifications regulate TMAO production, the impact of different intake methods, including oral gavage, dietary supplementation, and conditions such as fasting versus nonfasting, has not been fully explored. Twelve female Sprague-Dawley rats were divided into three diet groups (<em>n</em> = 4 per group): no-choline (0% choline), low-choline (0.08% choline), and high-choline (1% choline). Choline and TMAO fasting and nonfasting blood concentrations, and their kinetics following an acute choline challenge, were assessed before and after a 2-week dietary intervention with the distinct choline dietary levels. Fasting choline was under tight control, with little effect of dietary choline. Nonfasting choline was more variable, with high dietary choline reflected in higher blood choline. Greater levels of dietary choline were reflected in significantly greater levels of TMAO, particularly for nonfasting levels. Kinetic profiling demonstrated additional information regarding the appearance and clearance of these compounds from blood. These results suggest that acute oral choline gavage is likely most suitable for studies targeting acute (direct) inhibitors, whereas a choline-rich diet with assessment of fasting and nonfasting blood levels is more suitable for studying alterations to TMAO production capacity. Future research should examine the impact on atherosclerosis biomarkers and microbiome diversity to deepen the understanding of TMAO regulation and its cardiovascular implications.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109905"},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Bonfili , Francesco Maria Grasselli , Massimiliano Cuccioloni , Valentina Cecarini , Daniela Lufrano , Elena Vittadini , Livio Galosi , Gregorio Sonsini , Massimo Ubaldi , Jonathan Louis Turck , Luis Fernando da Costa Medina , Jan Suchodolski , Anna Maria Eleuteri
{"title":"A red lentils-based synbiotic cookie exerts neuroprotective effects in a mouse model of Alzheimer's disease","authors":"Laura Bonfili , Francesco Maria Grasselli , Massimiliano Cuccioloni , Valentina Cecarini , Daniela Lufrano , Elena Vittadini , Livio Galosi , Gregorio Sonsini , Massimo Ubaldi , Jonathan Louis Turck , Luis Fernando da Costa Medina , Jan Suchodolski , Anna Maria Eleuteri","doi":"10.1016/j.jnutbio.2025.109904","DOIUrl":"10.1016/j.jnutbio.2025.109904","url":null,"abstract":"<div><div>Gut microbiota preservation or rational manipulation is a key condition for healthy longevity and a promising strategy to prevent neurodegenerations exploiting the gut-brain axis, with a key role of prebiotics and probiotics. Whether their combination in a functional food can provide a synergistic effect to the host remains controversial. To fill this gap, we supplemented the diet of 3xTg-AD Alzheimer's disease mice with a red lentils (prebiotic)-based cookie enriched with neuroprotective probiotics and we performed behavioural, biochemical and molecular tests. Chronic consumption of this synbiotic preparation (functional cookie) preserved cognition, reduced amyloid load, improved glucose and lipid homeostasis and diminished oxidation and inflammation related damages compared to animals receiving a classic cookie (standard recipe). The synergistic effect was indicated by significantly higher glucose insulinotropic polypeptide concentrations in the functional cookie group compared to probiotic group. Moreover, Ruminoclostridium sp KB18 and Ruminicoccus decreased in the gut of mice supplemented with the functional cookie, partially explaining the improved short-term memory upon treatments and substantiating the combined use over individual components. This synbiotic innovative snack represents a prototype of a simple and affordable dietary approach to promote healthy aging and prevent or delay the onset of neurodegenerations.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109904"},"PeriodicalIF":4.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design and evaluation of curcumin-derived aldopentose compounds: Unlocking their antidiabetic potential through integrative in vitro, in vivo, and in silico studies on carbohydrate-degrading enzymes","authors":"Pedram Routabi , Maryam Mehrabi , Hadi Adibi , Masomeh Mehrabi , Reza Khodarahmi","doi":"10.1016/j.jnutbio.2025.109897","DOIUrl":"10.1016/j.jnutbio.2025.109897","url":null,"abstract":"<div><div>Natural polyphenol compounds such as curcumin can inhibit carbohydrate-hydrolyzing enzymes, which may offer an alternative to expensive and potentially side-effect-inducing α-glucosidase inhibitors like acarbose. Hence, this study carried out the synthesis of curcumin aldopentose derivatives, examining their capacity to inhibit the α-glucosidase and α-amylase enzymes with the aim to alleviate hyperglycemia. Initially, the aldopentose derivatives from curcumin were synthesized and confirmed by spectroscopic methods such as MS, <sup>13</sup>CNMR, <sup>1</sup>HNMR, and FTIR. Afterward, we investigated the inhibitory effects of all derivatives on the α-amylase and α-glucosidase enzymes spectroscopically and determined their inhibition mechanism. We assessed the antioxidant activity and the stability of the synthetic derivatives in the simulated intestinal environment. Finally, we measured the postprandial blood glucose level after administering saturated starch <em>in vivo</em>. The modified compounds showed improved inhibitory effects compared to curcumin alone, with compound C3 demonstrating particularly strong enzyme inhibition. However, when compared with acarbose, a known commercial antidiabetic drug, the synthetic compounds showed lower inhibitory activity against both enzymes, resulting in fewer side effects related to undigested polysaccharides in the gut. Molecular docking studies show introducing a pentose moiety to the curcumin backbone enhanced docking affinities toward both enzymes and subsequently altered the associated IC<sub>50</sub> and K<sub>i</sub> values. Overall, compound C3 has the potential to be an inhibitor of carbohydrate-degrading enzymes and can effectively reduce glucose absorption <em>in vivo</em>. Given its antioxidant capabilities and reasonable stability, the compound in question shows promises as a potent derivative for the development of new anti-hyperglycemic drugs in future research endeavours.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"141 ","pages":"Article 109897"},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}