Pub Date : 2025-12-25DOI: 10.1016/j.jnutbio.2025.110246
Shi-Ya Peng, Naihao Lu, Rong Tian
The interactions between L-ascorbic acid (i.e., Vitamin C, VC) and bovine hemoglobin (Hb) were comprehensively analyzed using fluorescence, circular dichroism, UV−vis absorption spectra and molecular docking method, to elucidate the structural mechanisms through which VC altered Hb redox states and stabilities. VC interacted with the central cavities of Hb to form Hb-VC complex via static quenching mechanism involving nonradiative energy transfer, with van der Waals forces and hydrogen bonds playing predominant roles in the binding processes. VC was surrounded by residues such as α1-Thr137, α1-Ser138, α1-Tyr140 and α1-Arg141 residues. After that, the binding of VC would narrow the crevices near the heme domain of Hb, which converted ferric (met-) Hb to ferrous (oxy-) Hb and deoxy-Hb state and suppressed hemin liberation (level of free hemin was 4.35 µM (Hb alone) and 2.77 µM (Hb-VC complex)). Moreover, VC significantly inhibited Hb-catalyzed lipid peroxidation in liposome and washed muscle, which was probably due to the conversion to oxy-Hb state and reduced dissociation of hemin (not free iron). In accordance with its effects on Hb redox states and stability, VC effectively maintained the red color of hemeprotein during the storage. Altogether, the attenuation of free hemin release from Hb molecule represents a new mechanism towards the anti-oxidant capacity of VC in Hb-containing foods.
{"title":"The interaction of ascorbic acid with hemoglobin: Relevance to hemin release and lipid peroxidation","authors":"Shi-Ya Peng, Naihao Lu, Rong Tian","doi":"10.1016/j.jnutbio.2025.110246","DOIUrl":"10.1016/j.jnutbio.2025.110246","url":null,"abstract":"<div><div>The interactions between L-ascorbic acid (<em>i.e.</em>, Vitamin C, VC) and bovine hemoglobin (Hb) were comprehensively analyzed using fluorescence, circular dichroism, UV−vis absorption spectra and molecular docking method, to elucidate the structural mechanisms through which VC altered Hb redox states and stabilities. VC interacted with the central cavities of Hb to form Hb-VC complex via static quenching mechanism involving nonradiative energy transfer, with van der Waals forces and hydrogen bonds playing predominant roles in the binding processes. VC was surrounded by residues such as α1-Thr137, α1-Ser138, α1-Tyr140 and α1-Arg141 residues. After that, the binding of VC would narrow the crevices near the heme domain of Hb, which converted ferric (met-) Hb to ferrous (oxy-) Hb and deoxy-Hb state and suppressed hemin liberation (level of free hemin was 4.35 µM (Hb alone) and 2.77 µM (Hb-VC complex)). Moreover, VC significantly inhibited Hb-catalyzed lipid peroxidation in liposome and washed muscle, which was probably due to the conversion to oxy-Hb state and reduced dissociation of hemin (not free iron). In accordance with its effects on Hb redox states and stability, VC effectively maintained the red color of hemeprotein during the storage. Altogether, the attenuation of free hemin release from Hb molecule represents a new mechanism towards the anti-oxidant capacity of VC in Hb-containing foods.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110246"},"PeriodicalIF":4.9,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846686","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}
Pub Date : 2025-12-24DOI: 10.1016/j.jnutbio.2025.110242
Elvira Marquez-Paradas , Maria Torrecillas-Lopez , Alfredo Corell-Almuraza , Teresa Gonzalez-de la Rosa , Luna Barrera-Chamorro , Beatriz Bermudez , Carmen M Claro-Cala , Sergio Montserrat-de la Paz
The postprandial period represents a critical and dynamic phase during which dietary components can acutely influence metabolic and immune functions. While the chronic effects of dietary fat quality are well characterized, their immediate postprandial immunometabolic impact remains poorly understood. To investigate the acute effects of energy-matched test meals enriched in saturated (SFA), monounsaturated (MUFA), or omega-3 long-chain polyunsaturated fatty acids (ω3-LCPUFA), compared to a fat-free control, on systemic metabolic and immune parameters in healthy adults. In this randomized, crossover pilot study, ten healthy participants consumed four test meals separated by 2-week washouts. Blood samples were collected at fasting, 2–3 h (peak), and 5–6 h (late phase) postprandially. Biochemical and immunological biomarkers were assessed. Statistical analyses included two-way repeated-measures ANOVA, linear mixed models, and area under the curve (AUC/iAUC) calculations. MUFA- and ω3-LCPUFA-enriched meals induced significantly greater postprandial changes in glucose, triacylglycerides, LDL-C, and C-peptide compared to the SFA and fat-free meals, particularly at the late postprandial phase. These effects were confirmed by AUC and iAUC analyses. In contrast, although transient changes in immune cell counts and humoral markers were observed over time, no significant differences between fat types were detected in postprandial immune responses. In healthy adults, the fatty acid composition of energy-matched meals acutely modulates key metabolic pathways in a fat-type-specific manner, whereas systemic immune parameters remain largely unchanged. These preliminary findings suggest a functional dissociation between postprandial metabolic and immune response and underscore the need to more sensitive or compartment-specific immune readouts in future nutritional research.
{"title":"Fatty acid composition of isoenergetic meals drives distinct postprandial immunometabolic responses in healthy adults: A randomized crossover pilot study","authors":"Elvira Marquez-Paradas , Maria Torrecillas-Lopez , Alfredo Corell-Almuraza , Teresa Gonzalez-de la Rosa , Luna Barrera-Chamorro , Beatriz Bermudez , Carmen M Claro-Cala , Sergio Montserrat-de la Paz","doi":"10.1016/j.jnutbio.2025.110242","DOIUrl":"10.1016/j.jnutbio.2025.110242","url":null,"abstract":"<div><div>The postprandial period represents a critical and dynamic phase during which dietary components can acutely influence metabolic and immune functions. While the chronic effects of dietary fat quality are well characterized, their immediate postprandial immunometabolic impact remains poorly understood. To investigate the acute effects of energy-matched test meals enriched in saturated (SFA), monounsaturated (MUFA), or omega-3 long-chain polyunsaturated fatty acids (ω3-LCPUFA), compared to a fat-free control, on systemic metabolic and immune parameters in healthy adults. In this randomized, crossover pilot study, ten healthy participants consumed four test meals separated by 2-week washouts. Blood samples were collected at fasting, 2–3 h (peak), and 5–6 h (late phase) postprandially. Biochemical and immunological biomarkers were assessed. Statistical analyses included two-way repeated-measures ANOVA, linear mixed models, and area under the curve (AUC/iAUC) calculations. MUFA- and ω3-LCPUFA-enriched meals induced significantly greater postprandial changes in glucose, triacylglycerides, LDL-C, and C-peptide compared to the SFA and fat-free meals, particularly at the late postprandial phase. These effects were confirmed by AUC and iAUC analyses. In contrast, although transient changes in immune cell counts and humoral markers were observed over time, no significant differences between fat types were detected in postprandial immune responses. In healthy adults, the fatty acid composition of energy-matched meals acutely modulates key metabolic pathways in a fat-type-specific manner, whereas systemic immune parameters remain largely unchanged. These preliminary findings suggest a functional dissociation between postprandial metabolic and immune response and underscore the need to more sensitive or compartment-specific immune readouts in future nutritional research.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110242"},"PeriodicalIF":4.9,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843726","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}
Unhealthy dietary patterns may impair renal function through elevated intake of methylglyoxal (MG) and advanced glycation end products (AGEs). While adipose tissue stores triglycerides (TG), its dysfunction promotes ectopic lipotoxicity, a process exacerbated by MG or AGEs. This study investigated if long-term dietary MG causes renal damage, mediated by adipose tissue dysfunction and ectopic lipid deposition. Eight-week-old male ICR mice were randomized into four groups for 52 weeks: normal diet and obesogenic high-fat diet (HFD), each with or without 1% MG in drinking water. Results showed that HFD significantly increased MG-AGEs in both adipose tissue and kidneys. Although HFD caused adipocyte hypertrophy and renal injury, no significant renal lipid accumulation was observed. In contrast, MG administration alone induced renal lipotoxicity and injury, manifested by increased TG concentrations in both the cortex and medulla. In HFD-fed mice, MG further exacerbated adipose tissue dysfunction by inhibiting angiogenesis and increasing interstitial collagen accumulation. Notably, the MG co-administration reduced adipocyte size, counteracting the hypertrophy caused by HFD alone. Furthermore, in the kidneys of these HFD-fed mice, MG led to increased medullary TG concentration and elevated collagen expression. In conclusion, HFD alone caused nonlipotoxic kidney injury without significant adipose dysfunction. However, MG administration consistently induced adipose tissue dysfunction and progressive renal lipotoxicity regardless of the diet. These findings suggest that MG-induced renal damage is primarily mediated by the dysfunction of adipose tissue, establishing a critical link between dietary MG intake and kidney disease progression, independent of obesogenic diet status.
{"title":"Dietary methylglyoxal induces renal lipotoxicity primarily through adipose tissue dysfunction in mice fed normal or obesogenic high-fat diets","authors":"Medhavi Paramita Kondanna , Yu-Ho Chang , Hsin-Yi Yang , Chi-Hao Wu , Wan-Ju Yeh","doi":"10.1016/j.jnutbio.2025.110244","DOIUrl":"10.1016/j.jnutbio.2025.110244","url":null,"abstract":"<div><div>Unhealthy dietary patterns may impair renal function through elevated intake of methylglyoxal (MG) and advanced glycation end products (AGEs). While adipose tissue stores triglycerides (TG), its dysfunction promotes ectopic lipotoxicity, a process exacerbated by MG or AGEs. This study investigated if long-term dietary MG causes renal damage, mediated by adipose tissue dysfunction and ectopic lipid deposition. Eight-week-old male ICR mice were randomized into four groups for 52 weeks: normal diet and obesogenic high-fat diet (HFD), each with or without 1% MG in drinking water. Results showed that HFD significantly increased MG-AGEs in both adipose tissue and kidneys. Although HFD caused adipocyte hypertrophy <strong>and</strong> renal injury, no significant renal lipid accumulation was observed. In contrast, MG administration alone induced renal lipotoxicity and injury, manifested by increased TG concentrations in both the cortex and medulla. In HFD-fed mice, MG further exacerbated adipose tissue dysfunction by inhibiting angiogenesis and increasing interstitial collagen accumulation. Notably, the MG co-administration reduced adipocyte size, counteracting the hypertrophy caused by HFD alone. Furthermore, in the kidneys of these HFD-fed mice, MG led to increased medullary TG concentration and elevated collagen expression. In conclusion, HFD alone caused nonlipotoxic kidney injury without significant adipose dysfunction. However, MG administration consistently induced adipose tissue dysfunction and progressive renal lipotoxicity regardless of the diet. These findings suggest that MG-induced renal damage is primarily mediated by the dysfunction of adipose tissue, establishing a critical link between dietary MG intake and kidney disease progression, independent of obesogenic diet status.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110244"},"PeriodicalIF":4.9,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843736","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}
The identification of novel long noncoding RNAs (lncRNAs) is involved in visceral adipose tissue development under fasting and refeeding conditions may be unravel the mechanisms of diet induced obesity. In this study, adult mice were subjected to fasting and refeeding intervention and mesenteric adipose tissue was extracted for transcriptome sequencing. Lnc-Gm26626 was identified and its role on tricarboxylic acid cycle (TCA) and isocitrate dehydrogenase 3α (IDH3α) expression was investigated using adenovirus-mediated gene interference. In vivo experiments were further performed to clarify whether lnc-Gm26626 affected the plasticity of adipose tissues. A total of 3,570 differentially expressed lncRNAs and 5,032 differentially expressed mRNAs were identified, lnc-Gm26626 was regulated by external nutritional stimulation and was observed to translocate from the nucleus to the cytoplasm under high glucose conditions. The knockdown of lnc-Gm26626 could inhibit the expression of IDH3α in vitro; AAV-mediated lnc-Gm26626 knockdown increased the fat content of mesenteric adipose tissues and alleviated the fluctuations in glucose and lipid metabolism during fasting and refeeding. Collectively, we identified lnc-Gm26626 as a novel regulator of energy metabolism that participate in the response to energy restriction by regulating IDH3α expression in the TCA cycle, thereby affecting visceral adipose tissue plasticity in male mice.
{"title":"Lnc-Gm26626 in visceral adipose tissues participates in energy metabolism via IDH3α-associated tricarboxylic acid cycle activity","authors":"Haoneng Tang , Fen Xiao , Yaru Chen , Chenyi Tang , Yue Guo , Huixuan Wu , Yinghui Zhou , Houde Zhou","doi":"10.1016/j.jnutbio.2025.110243","DOIUrl":"10.1016/j.jnutbio.2025.110243","url":null,"abstract":"<div><div>The identification of novel long noncoding RNAs (lncRNAs) is involved in visceral adipose tissue development under fasting and refeeding conditions may be unravel the mechanisms of diet induced obesity. In this study, adult mice were subjected to fasting and refeeding intervention and mesenteric adipose tissue was extracted for transcriptome sequencing. Lnc-Gm26626 was identified and its role on tricarboxylic acid cycle (TCA) and isocitrate dehydrogenase 3α (IDH3α) expression was investigated using adenovirus-mediated gene interference. <em>In vivo</em> experiments were further performed to clarify whether lnc-Gm26626 affected the plasticity of adipose tissues. A total of 3,570 differentially expressed lncRNAs and 5,032 differentially expressed mRNAs were identified, lnc-Gm26626 was regulated by external nutritional stimulation and was observed to translocate from the nucleus to the cytoplasm under high glucose conditions. The knockdown of lnc-Gm26626 could inhibit the expression of IDH3α in vitro; AAV-mediated lnc-Gm26626 knockdown increased the fat content of mesenteric adipose tissues and alleviated the fluctuations in glucose and lipid metabolism during fasting and refeeding. Collectively, we identified lnc-Gm26626 as a novel regulator of energy metabolism that participate in the response to energy restriction by regulating IDH3α expression in the TCA cycle, thereby affecting visceral adipose tissue plasticity in male mice.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110243"},"PeriodicalIF":4.9,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819694","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}
Pub Date : 2025-12-20DOI: 10.1016/j.jnutbio.2025.110240
Jiaming Ji , Jinyan Guo , Yin Huang , Ke Chen , Yuheng Xu , Weijian Liang , Zhenjia Lin , Chang Xiong , Xue Han , Jun Liu , Ziqing Hei , Sufang Chen , Weifeng Yao , Chaojin Chen
Electroconvulsive therapy (ECT) stands as the most effective intervention for treatment-resistant depression; however, its interaction with dietary regulation of the gut-brain axis has not been thoroughly explored. This study aimed to elucidate the mechanistic link between ECT, gut microbiota remodeling, short-chain fatty acid (SCFA) production, and neural plasticity. In this study, mice were subjected to chronic restraint stress (6 h/d for 28 consecutive days) to establish a depression-like model. Utilizing a translational approach that incorporated behavioral assessments, multimodal neuroimaging techniques such as PET-CT and laser speckle contrast imaging, along with multiomics analyses including metagenomics, metabolomics, and transcriptomics in rodent models, we demonstrated that ECT induced significant gut microbiota remodeling, characterized by an enrichment of SCFA-producing genera like Lactobacillus and Bifidobacterium. This remodeling was associated with restored intestinal barrier integrity and elevated plasma SCFA levels. Mechanistically, these microbial metabolites activated hippocampal Wnt/β-catenin signaling pathways, enhancing synaptic plasticity restoration, while concurrent probiotic supplementation further amplified brain-derived neurotrophic factor (BDNF) expression via SCFA-dependent epigenetic mechanisms. Neuroimaging corroborated the normalization of cerebral glucose metabolism and hemodynamic function post-ECT. In conclusion, our findings unveil a novel gut-brain communication pathway by which ECT exerts its antidepressant effects, positioning SCFAs as vital mediators connecting microbial metabolic alterations to neural plasticity. This research not only redefines the role of nutritional biochemistry in neuromodulation but also suggests the potential of microbial metabolite monitoring to tailor antidepressant therapies for enhanced efficacy.
{"title":"Electroconvulsive therapy modulates brain plasticity in male depression: Links to gut microbial metabolites and diet-derived regulation of Wnt/BDNF signaling","authors":"Jiaming Ji , Jinyan Guo , Yin Huang , Ke Chen , Yuheng Xu , Weijian Liang , Zhenjia Lin , Chang Xiong , Xue Han , Jun Liu , Ziqing Hei , Sufang Chen , Weifeng Yao , Chaojin Chen","doi":"10.1016/j.jnutbio.2025.110240","DOIUrl":"10.1016/j.jnutbio.2025.110240","url":null,"abstract":"<div><div>Electroconvulsive therapy (ECT) stands as the most effective intervention for treatment-resistant depression; however, its interaction with dietary regulation of the gut-brain axis has not been thoroughly explored. This study aimed to elucidate the mechanistic link between ECT, gut microbiota remodeling, short-chain fatty acid (SCFA) production, and neural plasticity. In this study, mice were subjected to chronic restraint stress (6 h/d for 28 consecutive days) to establish a depression-like model. Utilizing a translational approach that incorporated behavioral assessments, multimodal neuroimaging techniques such as PET-CT and laser speckle contrast imaging, along with multiomics analyses including metagenomics, metabolomics, and transcriptomics in rodent models, we demonstrated that ECT induced significant gut microbiota remodeling, characterized by an enrichment of SCFA-producing genera like <em>Lactobacillus</em> and <em>Bifidobacterium</em>. This remodeling was associated with restored intestinal barrier integrity and elevated plasma SCFA levels. Mechanistically, these microbial metabolites activated hippocampal Wnt/<em>β</em>-catenin signaling pathways, enhancing synaptic plasticity restoration, while concurrent probiotic supplementation further amplified brain-derived neurotrophic factor (BDNF) expression via SCFA-dependent epigenetic mechanisms. Neuroimaging corroborated the normalization of cerebral glucose metabolism and hemodynamic function post-ECT. In conclusion, our findings unveil a novel gut-brain communication pathway by which ECT exerts its antidepressant effects, positioning SCFAs as vital mediators connecting microbial metabolic alterations to neural plasticity. This research not only redefines the role of nutritional biochemistry in neuromodulation but also suggests the potential of microbial metabolite monitoring to tailor antidepressant therapies for enhanced efficacy.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110240"},"PeriodicalIF":4.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810429","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}
Pub Date : 2025-12-19DOI: 10.1016/j.jnutbio.2025.110234
Benjamin A. Levine , Alexis J. Lynch , Michael T. Bailey , Brett R. Loman
Dietary fiber ingestion serves as a critical regulator of intestinal motility and the structure and function of the enteric microbiome. Yet, the extent to which subtle structural differences among fibers modulate motility via microbiota-host interactions remains undefined. GABA is a microbial metabolite intimately related to microbial fructan fermentation and host intestinal motility. The purpose of this study was to investigate how fructan chain length influenced microbiota-host signaling underlying ileal and colonic contractions. Male and female mice were pair-fed diets containing no fiber (fiber-free diet, FFD) or the same diet containing cellulose (CELL, fiber control), short-chain fructooligosaccharides (scFOS), or inulin (INU) for 2 weeks. scFOS and INU similarly enhanced total microbial load (fluorescence in situ hybridization), relative abundances of GABA-synthesizing bacteria (16S rRNA sequencing), and luminal GABA concentrations (ELISA) in the ileum and colon versus FFD. Conversely, scFOS altered expression (Fluidigm qPCR) of more motility- and GABA-related genes than INU in the ileum, whereas INU altered expression of more motility and GABA-related genes than scFOS in the colon. Incubation of ileal segments with GABA potentiated contraction force in INU but not scFOS ex vivo. Conversely, incubation of colon segments with GABA repressed contraction force in scFOS, reducing them to levels observed in INU with or without GABA. Notably, GABA altered contraction forces only in female mice. Our study highlights dietary fructan chain length as a determinant of segment- and sex-specific GABA-mediated intestinal motility and creates a rationale and framework for investigation of how prebiotic fiber structures influence microbiota-host interactions and physiology.
{"title":"Prebiotic fructan chain length influences enteric microbiota-host GABAergic signaling and intestinal motility","authors":"Benjamin A. Levine , Alexis J. Lynch , Michael T. Bailey , Brett R. Loman","doi":"10.1016/j.jnutbio.2025.110234","DOIUrl":"10.1016/j.jnutbio.2025.110234","url":null,"abstract":"<div><div>Dietary fiber ingestion serves as a critical regulator of intestinal motility and the structure and function of the enteric microbiome. Yet, the extent to which subtle structural differences among fibers modulate motility via microbiota-host interactions remains undefined. GABA is a microbial metabolite intimately related to microbial fructan fermentation and host intestinal motility. The purpose of this study was to investigate how fructan chain length influenced microbiota-host signaling underlying ileal and colonic contractions. Male and female mice were pair-fed diets containing no fiber (fiber-free diet, FFD) or the same diet containing cellulose (CELL, fiber control), short-chain fructooligosaccharides (scFOS), or inulin (INU) for 2 weeks. scFOS and INU similarly enhanced total microbial load (fluorescence in situ hybridization), relative abundances of GABA-synthesizing bacteria (16S rRNA sequencing), and luminal GABA concentrations (ELISA) in the ileum and colon versus FFD. Conversely, scFOS altered expression (Fluidigm qPCR) of more motility- and GABA-related genes than INU in the ileum, whereas INU altered expression of more motility and GABA-related genes than scFOS in the colon. Incubation of ileal segments with GABA potentiated contraction force in INU but not scFOS ex vivo. Conversely, incubation of colon segments with GABA repressed contraction force in scFOS, reducing them to levels observed in INU with or without GABA. Notably, GABA altered contraction forces only in female mice. Our study highlights dietary fructan chain length as a determinant of segment- and sex-specific GABA-mediated intestinal motility and creates a rationale and framework for investigation of how prebiotic fiber structures influence microbiota-host interactions and physiology.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110234"},"PeriodicalIF":4.9,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805016","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}
Pub Date : 2025-12-19DOI: 10.1016/j.jnutbio.2025.110241
Chengming Hu , Changle Dong , Huimin Yang , Zejun Yu , Yang Li , Yinsheng Qiu , Zhinan Mei , Lingyun Xu
Hyperuricemic nephropathy (HN) is a serious kidney complication of hyperuricemia, yet effective treatments are lacking. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been implicated in renal tubular injury, but its regulatory mechanisms in HN remain unclear. This study investigated the protective effects of diosmetin (DIOS), a natural flavonoid with antioxidant properties, against monosodium urate (MSU)-induced damage in HK-2 human renal tubular cells. We confirmed that MSU-induced cell death was characteristic of ferroptosis. Through a combination of transcriptomic analysis and network pharmacology, we identified the BNIP3/Nrf2/GPX4 pathway as the primary potential target of DIOS. Molecular docking and subsequent experimental validation demonstrated that DIOS directly interacts with and modulates BNIP3, leading to the activation of Nrf2 and the upregulation of its downstream target, GPX4. This cascade enhanced the cellular antioxidant defense system, effectively suppressing lipid peroxidation and ferroptosis. Our findings reveal a novel mechanism by which DIOS protects against MSU-induced renal tubular injury and highlight the BNIP3/Nrf2/GPX4 axis as a promising therapeutic target for mitigating ferroptosis in HN.
{"title":"Diosmetin alleviates hyperuricemic nephropathy by activating the BNIP3/Nrf2/GPX4 pathway to inhibit ferroptosis of renal tubular epithelial cells induced by monosodium urate crystals","authors":"Chengming Hu , Changle Dong , Huimin Yang , Zejun Yu , Yang Li , Yinsheng Qiu , Zhinan Mei , Lingyun Xu","doi":"10.1016/j.jnutbio.2025.110241","DOIUrl":"10.1016/j.jnutbio.2025.110241","url":null,"abstract":"<div><div>Hyperuricemic nephropathy (HN) is a serious kidney complication of hyperuricemia, yet effective treatments are lacking. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been implicated in renal tubular injury, but its regulatory mechanisms in HN remain unclear. This study investigated the protective effects of diosmetin (DIOS), a natural flavonoid with antioxidant properties, against monosodium urate (MSU)-induced damage in HK-2 human renal tubular cells. We confirmed that MSU-induced cell death was characteristic of ferroptosis. Through a combination of transcriptomic analysis and network pharmacology, we identified the BNIP3/Nrf2/GPX4 pathway as the primary potential target of DIOS. Molecular docking and subsequent experimental validation demonstrated that DIOS directly interacts with and modulates BNIP3, leading to the activation of Nrf2 and the upregulation of its downstream target, GPX4. This cascade enhanced the cellular antioxidant defense system, effectively suppressing lipid peroxidation and ferroptosis. Our findings reveal a novel mechanism by which DIOS protects against MSU-induced renal tubular injury and highlight the BNIP3/Nrf2/GPX4 axis as a promising therapeutic target for mitigating ferroptosis in HN.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110241"},"PeriodicalIF":4.9,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805018","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}
Pub Date : 2025-12-17DOI: 10.1016/j.jnutbio.2025.110238
Saurabh Kumar Kaushal , Devendra Pratap Singh , Ankita Paul , Megha Dixit , Divya Singh
Naringenin is a plant-derived flavonoid having anti-proliferative, anti-inflammatory, and anti-angiogenic properties against various metabolic disorders. Though there are reports demonstrating the osteogenic potential of naringenin, its effect remains largely unexplored in senile osteoporosis. The current study was planned with the objective to demonstrate the osteoprotective effect of naringenin in conditions of senile osteoporosis induced by d-galactose (D-gal). The results in the d-gal aging bone loss animal model suggest that naringenin improves bone microarchitecture, promotes ex-vivo mineralization, and alters bone serum markers. To check the mode of action of naringenin behind its protective effect, further experiments were performed at the cellular level. Naringenin facilitates osteoblast differentiation and suppresses osteoblast senescence, apoptosis, and cellular reactive oxygen species production in primary osteoblast cells after d-gal stimulation. Mechanistically, naringenin mitigates senescence through the estrogen receptor-mediated pathway, as confirmed when calvarial osteoblast cells treated with ICI182.780, an estrogen pathway inhibitor, greatly decrease its effectiveness. Taken together, these results lead us to conclude that naringenin may function as a potential therapeutic agent for senile osteoporosis.
{"title":"Naringenin prevents osteoblast senescence in d-galactose-induced aging conditions via estrogen receptor-mediated pathway","authors":"Saurabh Kumar Kaushal , Devendra Pratap Singh , Ankita Paul , Megha Dixit , Divya Singh","doi":"10.1016/j.jnutbio.2025.110238","DOIUrl":"10.1016/j.jnutbio.2025.110238","url":null,"abstract":"<div><div>Naringenin is a plant-derived flavonoid having anti-proliferative, anti-inflammatory, and anti-angiogenic properties against various metabolic disorders. Though there are reports demonstrating the osteogenic potential of naringenin, its effect remains largely unexplored in senile osteoporosis. The current study was planned with the objective to demonstrate the osteoprotective effect of naringenin in conditions of senile osteoporosis induced by <span>d</span>-galactose (D-gal). The results in the <span>d</span>-gal aging bone loss animal model suggest that naringenin improves bone microarchitecture, promotes ex-vivo mineralization, and alters bone serum markers. To check the mode of action of naringenin behind its protective effect, further experiments were performed at the cellular level. Naringenin facilitates osteoblast differentiation and suppresses osteoblast senescence, apoptosis, and cellular reactive oxygen species production in primary osteoblast cells after <span>d</span>-gal stimulation. Mechanistically, naringenin mitigates senescence through the estrogen receptor-mediated pathway, as confirmed when calvarial osteoblast cells treated with ICI182.780, an estrogen pathway inhibitor, greatly decrease its effectiveness. Taken together, these results lead us to conclude that naringenin may function as a potential therapeutic agent for senile osteoporosis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110238"},"PeriodicalIF":4.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794207","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}
Pub Date : 2025-12-16DOI: 10.1016/j.jnutbio.2025.110239
Jingyi Ren , Xiaoxin Jiang , Gejun Yu , Wentao Wu , Mengyuan Chen , Yun Zhao , Mengjie Yang , Zuquan Zou , Canxia He
Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has shown therapeutic potential in inflammatory diseases. Our previous studies demonstrated that SFN ameliorates ulcerative colitis (UC) and restores gut microbiota composition in dextran sulfate sodium (DSS)-induced mice. In the present study, we further investigate the protective effects and underlying mechanisms of SFN against secondary liver injury associated with UC. The results revealed that SFN significantly alleviated pathological damage in both the colon and liver, improved liver function parameters, upregulated intestinal tight junction proteins and Muc2 expression, and inhibited inflammation in DSS-induced colitis mice. Additionally, SFN significantly elevated short-chain fatty acid (SCFA) concentrations, enhanced the expression of SCFA receptors (free fatty acid receptors 2 and 3, FFAR2/3), and modulated macrophage polarization by inhibiting M1 and promoting M2 phenotypes in the colon and liver. Collectively, these findings suggest that SFN may alleviate colitis and secondary liver injury by enhancing intestinal barrier function and reducing inflammatory responses, potentially via the SCFAs-FFAR2/3-macrophage polarization signaling cascade. Thus, SFN may serve as a promising adjunctive therapeutic agent for the prevention and treatment of UC.
{"title":"Sulforaphane ameliorates DSS-induced colitis and secondary liver injury in mice: Proposed mechanism in the SCFAs-FFAR2/3-macrophage polarization axis","authors":"Jingyi Ren , Xiaoxin Jiang , Gejun Yu , Wentao Wu , Mengyuan Chen , Yun Zhao , Mengjie Yang , Zuquan Zou , Canxia He","doi":"10.1016/j.jnutbio.2025.110239","DOIUrl":"10.1016/j.jnutbio.2025.110239","url":null,"abstract":"<div><div>Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has shown therapeutic potential in inflammatory diseases. Our previous studies demonstrated that SFN ameliorates ulcerative colitis (UC) and restores gut microbiota composition in dextran sulfate sodium (DSS)-induced mice. In the present study, we further investigate the protective effects and underlying mechanisms of SFN against secondary liver injury associated with UC. The results revealed that SFN significantly alleviated pathological damage in both the colon and liver, improved liver function parameters, upregulated intestinal tight junction proteins and Muc2 expression, and inhibited inflammation in DSS-induced colitis mice. Additionally, SFN significantly elevated short-chain fatty acid (SCFA) concentrations, enhanced the expression of SCFA receptors (free fatty acid receptors 2 and 3, FFAR2/3), and modulated macrophage polarization by inhibiting M1 and promoting M2 phenotypes in the colon and liver. Collectively, these findings suggest that SFN may alleviate colitis and secondary liver injury by enhancing intestinal barrier function and reducing inflammatory responses, potentially via the SCFAs-FFAR2/3-macrophage polarization signaling cascade. Thus, SFN may serve as a promising adjunctive therapeutic agent for the prevention and treatment of UC.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110239"},"PeriodicalIF":4.9,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781376","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}
Determining dietary energy and protein level to accelerate heifer growth while ensuring mammary development remains challenging. Technical and economic constraints in cattle hinder defining optimal energy protein levels and breeding timing. Thus, we used mice as a model to examine how post-weaning diets differing in energy and protein concentrations, combined with two breeding strategies, affect mammary development and lactation. Two hundred forty female mice (21 d) were divided into five dietary groups: high-energy moderate-protein, high-energy low-protein, moderate-energy moderate-protein, low-energy moderate-protein and low-energy low-protein. Mammary tissue and serum were collected at target mating weight (27±1 g) and body maturity (56 d). Breeding was initiated either upon attainment of target weight or at 63 d of age, with collection of mammary and serum samples at gestation 15 d as well as serum samples at lactation 13 d. The results showed that moderate increases in dietary energy accelerate growth, enhance mammary development, and improve lactational performance in mice. Under low-energy intake, maintaining adequate protein is critical for mammary and overall growth. High-energy feeding combined with a weight-based mating strategy markedly increased milk yield, whereas age-based mating provided nutrient-restricted mice with the necessary developmental window. These findings provide a theoretical foundation for advancing age at first calving through high energy feeding strategies in heifer management.
{"title":"Effects of pubertal dietary energy-protein levels and breeding strategies on mammary gland development and lactational performance in mice","authors":"Xusheng Dong , Siyu Tian , Wenjing Yu, Xueyan Lin, Zhonghua Wang, Qiuling Hou","doi":"10.1016/j.jnutbio.2025.110236","DOIUrl":"10.1016/j.jnutbio.2025.110236","url":null,"abstract":"<div><div>Determining dietary energy and protein level to accelerate heifer growth while ensuring mammary development remains challenging. Technical and economic constraints in cattle hinder defining optimal energy protein levels and breeding timing. Thus, we used mice as a model to examine how post-weaning diets differing in energy and protein concentrations, combined with two breeding strategies, affect mammary development and lactation. Two hundred forty female mice (21 d) were divided into five dietary groups: high-energy moderate-protein, high-energy low-protein, moderate-energy moderate-protein, low-energy moderate-protein and low-energy low-protein. Mammary tissue and serum were collected at target mating weight (27±1 g) and body maturity (56 d). Breeding was initiated either upon attainment of target weight or at 63 d of age, with collection of mammary and serum samples at gestation 15 d as well as serum samples at lactation 13 d. The results showed that moderate increases in dietary energy accelerate growth, enhance mammary development, and improve lactational performance in mice. Under low-energy intake, maintaining adequate protein is critical for mammary and overall growth. High-energy feeding combined with a weight-based mating strategy markedly increased milk yield, whereas age-based mating provided nutrient-restricted mice with the necessary developmental window. These findings provide a theoretical foundation for advancing age at first calving through high energy feeding strategies in heifer management.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110236"},"PeriodicalIF":4.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774712","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}
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