Journal of Nutritional Biochemistry最新文献

{"title":"Folic acid supplementation inhibits autophagy-dependent apoptosis in rat brain neural cells and HT-22 neurons via the p53/mTOR signaling pathway.","authors":"Qinghan Ren, Jing Zhao, Yunfei Ma, Tongtong Li, Xin He, Jing Yan, Guowei Huang, Wen Li, Zhenshu Li","doi":"10.1016/j.jnutbio.2025.110014","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110014","url":null,"abstract":"<p><p>Folic acid (FA) can modulate neurogenesis and neural cell death, including autophagy and apoptosis, crucial for maintaining neurological homeostasis. Previous studies on the relationship between autophagy and apoptosis were contradictory, and the study aimed to investigate FA's impact on these processes in neural cells and the mechanisms involved. Three-week-old Sprague Dawley (SD) rats were divided into four dietary groups based on FA intake: FA-deficient (< 0.1 mg/kg), FA-normal (2 mg/kg), low FA-supplemented (4.0 mg/kg), and high FA-supplemented (8.0 mg/kg), with dietary treatments for 11 months. Neural cell apoptosis was quantified using TdT-mediated dUTP nick end labelling (TUNEL) assay, and autophagy-associated protein microtubule-associated light chain 3 (LC3)/Beclin-1 expression was detected by immunofluorescence (IF). HT-22 neurons were incubated with 1, 10, 20, and 40 μmol/L FA for 2, 4 and 8 d. Cell apoptosis was detected by flow cytometry, autophagic vacuoles were assessed by monodansyl cadaverine (MDC) assay, and the expression of autophagy-related proteins LC3/Beclin-1/p62 and p53/mammalian target of rapamycin (mTOR) pathway was analyzed by Western blotting (WB). In vivo, FA supplementation downregulated the autophagy-associated protein LC3/Beclin-1 expression in rat neural cells, further inhibiting apoptosis, whereas FA deficiency exhibited the opposite effect. In vitro study further revealed that FA supplementation reduced autophagy-dependent apoptosis in HT-22 neurons with decreased p53 expression and increased mTOR expression in a dose-dependent manner within the specific range. These results suggest that FA supplementation may inhibit autophagy-dependent apoptosis in neural cells via the p53/mTOR signaling pathway, whereas FA deficiency produced a significantly negative effect.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110014"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553794","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":"Impact of infant nutrition on gut and brain nitrogenous metabolomes: Comparison of human milk and infant formula feeding in the minipiglet model.","authors":"Elise Charton, Karl Fraser, Paul J Moughan, Carlos A Montoya, Milson Francis, Amandine Bellanger, Nicole C Roy, Didier Dupont, Amélie Deglaire, Isabelle Le Huërou-Luron","doi":"10.1016/j.jnutbio.2025.110015","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110015","url":null,"abstract":"<p><p>The effect of infant nutrition on the metabolism of different body compartments is poorly described. Hence, the present study aimed to characterize the effect of human milk (HM) vs. infant formula (IF) feeding on metabolic mediators in key samples crucial for metabolic activity through the gut-brain axis during infant development, using the minipiglet as a human infant model. Eighteen 19-day-old piglets were fed HM or IF for six days. Thirty min after the last meal, colonic digesta, blood plasma, liver and six regions of the brain were sampled. Profiles of 45 metabolites (including proteinous amino acids, tryptophan (Trp) metabolites, polyamines, neurotransmitters) were determined using a targeted liquid chromatography and tandem mass spectrometry approach. Metabolic signatures of key organs involved in the gut-brain signal exchange were diet-dependent. The main dietary-induced differences in metabolite content occurred in the hippocampus (77% of the targeted metabolites quantified), plasma (47%), brainstem (17%), and colonic digesta (16%). These differences concerned Trp, Trp-derived metabolites, polyamines, some proteinous amino acids and neurotransmitters. Tryptophan was preferentially metabolized towards the kynurenine pathway in the colon and the hippocampus of HM-fed piglets. Differences in brain amino acid levels were associated with different brain polyamine and neurotransmitter contents in the hippocampus and, to a lower extent, in the other brain regions. Significant (P<0.05) correlations with specific bacterial genera and gene expressions were found. In the colon, Trp-derived metabolites such as kynurenine and tryptamine were positively and negatively correlated with Veillonella, respectively, and tryptamine levels may be related to the abundance of Ruminococcus genera. In the brain, the elevated level of the 5-hydroxyindolacetic acid (5-HIAA, from the serotonine pathway) in the HM brainstem may be related to the more abundant Bifidobacterium in HM-fed piglets. Finally, bacteria from the Firmicutes and Proteobacteria phyla may be involved in modulating polyamine production, as suggested by significant correlations between polyamine levels and bacterial genus abundances in the colon. Overall, the results confirmed the differential effect of HM vs. IF feeding on the microbiota-gut-brain axis and showed the high metabolic responsiveness of the hippocampus, probably related to specific nutritional needs and functionality in minipiglets.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110015"},"PeriodicalIF":4.8,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528386","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":"The modulation of mTOR signaling on dietary carbohydrate utilization in largemouth bass (Micropterus salmoides)","authors":"Meidong Lv ,&nbsp;Kang Yang ,&nbsp;Xuan Wang ,&nbsp;Chengdong Liu ,&nbsp;Huihui Zhou ,&nbsp;Kangsen Mai ,&nbsp;Gen He","doi":"10.1016/j.jnutbio.2025.110008","DOIUrl":"10.1016/j.jnutbio.2025.110008","url":null,"abstract":"<div><div>Glucose intolerance is prevalent in teleost fish species, making them prone to dietary carbohydrate-induced fatty liver disease. However, the underlying mechanism is not well understood. In the present study, the possible role of mTOR signaling in the regulation of glucose metabolism was examined in largemouth bass (<em>Micropterus salmoides</em>), an economically important carnivorous aquaculture species. An 8-wk feeding trial was conducted with largemouth bass, in which they were fed different isonitrogenous and isolipidic diets supplemented with leucine (Leu), rapamycin (Rap), or an mTOR activator (mTOR-S). The results demonstrated that mTOR stimulation significantly enhanced the growth performance and feed utilization, while mTOR inhibition had the opposite effect in largemouth bass. More importantly, mTOR stimulation significantly reduced plasma glucose levels and concomitantly increased insulin levels. Furthermore, mTOR stimulation increased glycolysis and TCA cycle activities, augmented hepatic ATP levels and suppressed AMPK phosphorylation. Accordingly, mTOR stimulation also reduced SREBP1 activity, decreased hepatic lipid content and increased glycogen content. These results demonstrated that mTOR stimulation could promote postprandial glucose utilization in largemouth bass. This could provide a new strategy for improving dietary carbohydrate tolerance in aquaculture feed formulation.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110008"},"PeriodicalIF":4.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506015","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":"Naringenin attenuates slow-transit constipation by regulating the AMPK/mTOR/ULK1 signaling pathway: In vivo and in vitro studies.","authors":"Yahui Wang, Xiaopeng Wang, Yifei Qian, Mingming Sun, Huiju Yang, Lianlin Su, Shuai Yan","doi":"10.1016/j.jnutbio.2025.110013","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110013","url":null,"abstract":"<p><p>Slow-transit constipation (STC) is a widespread functional gastrointestinal condition distinguished by decreased colonic motility as an essential clinical characteristic. The excessive autophagy of interstitial cells of Cajal (ICCs) causes phenotypic changes and functional abnormalities, which are important in colonic dysmotility. Naringenin (NAR) has been shown to regulate gastrointestinal motility disorders. The present study aimed to elucidate the regulatory role of NAR in autophagy in STC and its underlying mechanism. Loperamide (Lop)-induced ICCs from STC mice and L-Glutamic acid (GA)-induced ICCs from rats were utilized as in vivo and in vitro models. The experiments involved various techniques, such as flow cytometry, Western blotting, CCK-8 assay, siRNA transfection, real-time PCR (RT-qPCR), co-immunoprecipitation, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), histological analysis, transmission electron microscopy (TEM), and immunohistochemistry (IHC). Our results indicated that NAR improved the survival and apoptosis of ICCs after GA by inhibiting autophagy through the partial suppression of the AMPK/mTOR/ULK1 signaling pathway Western blot analysis revealed that NAR treatment significantly reduced phosphorylation ratios of key autophagy regulators: pT172-AMPK/AMPK, pS2448-mTOR/mTOR, and pS757-ULK1/ULK1 in ICCs after GA. Critically, the level of pS757-ULK1 demonstrated a strong mechanistic association with autophagic initiation and modulation. NAR inhibits the autophagic degradation of pS757-ULK1 by weakening the interactions between pS757-ULK1 and the selective autophagy receptor genes NDP52 or OPTN. Further research revealed that NAR significantly increased fecal moisture content and small intestinal propulsion rate in constipated mice, while elevating serum excitatory neurotransmitters (GAS, 5-HT, MTL, SP) and reducing inhibitory neurotransmitters (VIP, SS). Additionally, it ameliorated pathological damage in Lop-induced STC mice and upregulated ANO1 and c-Kit expression in colonic tissues. Its molecular mechanism is consistent with the in vitro results. In summary, NAR inhibits excessive autophagy in ICC through the AMPK/mTOR/ULK1 pathway, thereby improving STC colonic dysmotility and underscoring its promise as a therapeutic option for STC.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110013"},"PeriodicalIF":4.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506014","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":"Myo-inositol supplementation in diet-induced obese lactating rats mitigates metabolic dysregulation and improves offspring health in early life","authors":"Ana Valle ,&nbsp;Bàrbara Reynés ,&nbsp;Andrei Petre-Munteanu ,&nbsp;Andreu Palou ,&nbsp;Catalina Picó ,&nbsp;Mariona Palou","doi":"10.1016/j.jnutbio.2025.110012","DOIUrl":"10.1016/j.jnutbio.2025.110012","url":null,"abstract":"<div><div>Myo-inositol (MI) supplementation has emerged as a promising intervention to mitigate the malprogramming effects associated with adverse maternal conditions during the perinatal period. This study aimed to assess the effects of MI supplementation during lactation on metabolism in diet-induced obese rats and on early health outcomes in their offspring. Female Wistar rats were fed either a control (CON) or Western diet (WD) for one month before mating and during gestation and lactation. After parturition, dams were supplemented daily with either MI or vehicle (V) throughout lactation. Phenotypic traits, along with milk and blood parameters were analyzed in dams and their offspring during lactation. At weaning, hepatic lipid content and gene expression in the liver, retroperitoneal white adipose tissue (rWAT), and mammary gland were assessed in dams. MI supplementation significantly reduced hepatic lipid accumulation in WD-dams and decreased pro-inflammatory markers in the liver (<em>Tnfa</em>) and retroperitoneal white adipose tissue (rWAT) (<em>Tnfa, Il6</em>) in both CON- and WD-dams, as well as modulated milk insulin levels. Their offspring exhibited, in plasma, higher MI and BDNF concentrations as well as lower insulin levels, which are key factors in perinatal programming. These findings suggest that maternal MI supplementation during lactation confers metabolic benefits to both dams and their offspring, specifically improving maternal inflammation and lipid metabolism while influencing milk composition.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110012"},"PeriodicalIF":4.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340220","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":"Ergothioneine as a functional nutraceutical: Mechanisms, bioavailability, and therapeutic implications","authors":"Rony Abdi Syahputra ,&nbsp;Amer Ahmed ,&nbsp;Asriadi ,&nbsp;Arnika Gloria Br. Sitorus ,&nbsp;Sintia Karina Putri ,&nbsp;Michle William Tan ,&nbsp;Qhelen Mayline Chandra ,&nbsp;Brathennovic ,&nbsp;Yumiko Angiosaki ,&nbsp;Felice Chrismary Lu ,&nbsp;Davini Clister ,&nbsp;Arya Tjipta Prananda ,&nbsp;Princella Halim ,&nbsp;Rosy Iara Maciel de Azambuja Ribeiro ,&nbsp;Fahrul Nurkolis ,&nbsp;Aminah Dalimunthe","doi":"10.1016/j.jnutbio.2025.110006","DOIUrl":"10.1016/j.jnutbio.2025.110006","url":null,"abstract":"<div><div>Ergothioneine (EGT), a naturally occurring sulfur-containing antioxidant, has gained significant attention owing to its potent cytoprotective, anti-inflammatory, and neuroprotective properties. As a dietary-derived compound predominantly found in mushrooms, EGT exhibits remarkable stability and bioavailability, facilitated by a specific ergothioneine transporter that is highly expressed in mammalian tissues. Its ability to scavenge reactive oxygen and nitrogen species effectively mitigates oxidative stress, which is a key factor in the pathogenesis of various chronic diseases, including cardiovascular disorders, neurodegenerative conditions, and cancer. Emerging evidence has highlighted the role of EGT in modulating key signaling pathways involved in inflammation, apoptosis, and cellular homeostasis, suggesting its potential as a therapeutic agent. Clinical and preclinical studies have indicated its involvement in metabolic regulation, endothelial protection, and attenuation of neurodegeneration, further reinforcing its significance as a functional nutraceutical agent. This review provides a comprehensive analysis of EGT, including its biosynthesis, dietary sources, absorption mechanisms, and metabolism, and elucidates its therapeutic potential and mechanistic underpinnings for disease prevention and management. By summarizing recent advances in EGT research, this review aims to guide future investigations and support its broader application in clinical and nutritional sciences.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110006"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336658","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":"Untargeted metabolomics reveals the mechanisms of luteolin and exercise combination treatment against cognitive impairments in AD mice through modulating autophagy","authors":"Xue Tao ,&nbsp;Liguo Wang ,&nbsp;Weijun Gong","doi":"10.1016/j.jnutbio.2025.110011","DOIUrl":"10.1016/j.jnutbio.2025.110011","url":null,"abstract":"<div><div>Alzheimer's disease (AD) yields a dramatic burden on patients and their families, with no complete cure yet. Our group has previously found that AD-related cognitive impairment (ARCI) could be alleviated after luteolin and exercise combination treatment (Lut + Exe), but the potential mechanisms require further exploration. This work used untargeted metabolomics to uncover the mechanisms Lut + Exe protects against ARCI. Utilizing an Aβ_1-42-oligomers-induced AD model, the Morris water maze (MWM) test was performed. Metabolomics of plasma was performed to identify differential metabolites. KEGG and MetaboAnalyst were used to enrich the metabolic pathways. Then, the autophagy inhibitor chloroquine (CQ) was utilized to verify the potential role of autophagy in the Lut+ Exe efficacy against ARCI. The results showed that Lut + Exe alleviated the ARCI in mice. The in-depth analysis showed that Lut + Exe could significantly affect purine metabolism, retinol metabolism, thiamine metabolism, histidine metabolism, and cysteine and methionine metabolism, indicating that the energy metabolism disorder was alleviated. Based on the close relationship between autophagy and energy metabolism, further study found that Lut + Exe could reverse the significant reduction of key autophagy proteins of AD model mice, while the effects of it on the MWM performance and neurogenesis of AD model mice could be blocked by CQ. This study reveals the crucial role of autophagy in the mechanisms of Lut + Exe against ARCI using untargeted metabolomics. Our work provides a novel paradigm to promote the use of combination treatment in curing AD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110011"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336660","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":"AMPK-mediated energy metabolism disorders are associated with impaired type IIB muscle fiber regeneration in broiler chickens with wooden breast myopathy","authors":"Qin-Jian Niu ,&nbsp;Jia-Cheng Yang ,&nbsp;Rong-Hui Huang,&nbsp;Zhi-Yuan Xia,&nbsp;Alainaa Refaie,&nbsp;Lv-Hui Sun","doi":"10.1016/j.jnutbio.2025.110009","DOIUrl":"10.1016/j.jnutbio.2025.110009","url":null,"abstract":"<div><div>Wooden breast (WB) myopathy is a myodegenerative muscle disease, in which muscle regeneration is also commonly observed, and has been increasingly reported in fast-growing broilers in recent years. This study aims to investigate the underlying mechanism of energy metabolism abnormalities on muscle regeneration in WB. A total of 300 male Ross 308 broilers were evaluated at 42 days of age based on physical and biochemical examinations to classify the severity of WB. From these, 16 broilers were selected for each of three groups: the normal group (CON), the moderate WB group (WB-M), and the severe WB group (WB-S). Compared to CON, WB were heavier, thicker, harder and had lower meat quality. Additionally, WB exhibited disturbance of energy metabolism, with increased cholesterol and triglycerides and decreased glycogen and lactate contents. Meanwhile, WB exhibited muscle regeneration as illustrated by the increased central nuclei and inflammation cells in muscle and higher creatine kinase activity in serum and muscle. WB exhibited inhibition of AMPK activity, with lower phosphorylation at Thr172 and higher phosphorylation at Ser496. Consistently, WB dysregulated the downstream pathways of AMPK, such as protein synthesis activity, glycolysis activity, lipid metabolism activity, and inflammatory response. Furthermore, in primary myoblasts, AMPK activation suppressed type II B myofiber hypertrophy, while its inhibition enhanced hypertrophy. In conclusion, this study provides evidence that abnormal ⅡB myofiber regeneration associated with imbalance in AMPK-mediated energy homeostasis, plays a crucial role in the pathogenesis of WB. These finding may provide new insights into mitigating the onset of WB.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110009"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336657","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":"Ferulic acid ethyl ester modulates electrical remodeling in cardiomyocytes exposed to TNF-α-stimulated adipocyte secretome via Nrf2/HO-1 pathway","authors":"Hsiang-Yu Yang ,&nbsp;Kwok-Keung Lam ,&nbsp;Chien-Ju Chou ,&nbsp;Bo-Yao Wen ,&nbsp;Chung-Bai Wang ,&nbsp;Yen-Mei Lee ,&nbsp;Chih-Yuan Lin ,&nbsp;Pao-Yun Cheng","doi":"10.1016/j.jnutbio.2025.110005","DOIUrl":"10.1016/j.jnutbio.2025.110005","url":null,"abstract":"<div><div>Inflammatory epicardial adipose tissue impacts cardiomyocytes, creating an arrhythmogenic substrate. This study examines the effects of tumor necrosis factor-α (TNF-α)-stimulated adipocytes on atrial cardiomyocytes and the protective role of ferulic acid ethyl ester (FAEE). TNF-α-stimulated 3T3-L1-derived adipocytes were utilized and analyzed. Conditioned media from TNF-α-stimulated and TNF-α/FAEE-cotreated adipocytes were examined. Biochemical and electrophysiological studies were performed on HL-1 myocytes exposed to these media. TNF-α stimulation increased the levels of the proinflammatory proteins monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in the adipocytes and conditioned media. The ratio of phosphorylated-NF-κB (pNF-κB) to NF-κB was higher in TNF-α-stimulated adipocytes than in the control group. While the levels of IL-6, MCP-1, and pNF-κB induced by TNF-α stimulation in the adipocytes remained unchanged with FAEE cotreatment, FAEE increased the protein levels of adiponectin in the adipocytes and the conditioned medium. FAEE also upregulated the protein levels of heme-oxygenase 1 (HO-1) and nuclear translocation of nuclear factor-erythroid 2-related factor-2 (Nrf2). The elevated adiponectin levels observed in FAEE-cotreated adipocytes were abolished following treatment with SnPP, a HO-1 inhibitor. The elevated levels of Ca²⁺/calmodulin-dependent protein kinase II and connexin 43, and the enhanced reverse mode Na⁺–Ca²⁺ exchanger current observed in HL-1 myocytes cultured in TNF-α-conditioned medium were abolished when these cardiomyocytes were cultured in TNF-α/FAEE-conditioned medium. FAEE modulates the electrical remodeling of HL-1 cardiomyocytes induced by the secretome of TNF-α-stimulated adipocytes, possibly through Nrf2/HO-1 signaling and adiponectin expression. These findings demonstrate FAEE's cardioprotective mechanisms and therapeutic potential.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110005"},"PeriodicalIF":4.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336659","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":"The impact of pasture-fed versus total mixed ration derived whole milk powder (WMP) on circulating fatty acid concentrations and cardiometabolic health in healthy adults: Results from a randomized controlled crossover trial","authors":"Martina Rooney ,&nbsp;Aileen O’Connor ,&nbsp;Clare Gollogly ,&nbsp;Andrea Mills ,&nbsp;Simone Dunne ,&nbsp;Clíona Ní Chonnacháin ,&nbsp;Mark Timlin ,&nbsp;André Brodkorb ,&nbsp;Tom F. O’Callaghan ,&nbsp;Jonathan B. Magan ,&nbsp;John Tobin ,&nbsp;Michael O’Donovan ,&nbsp;Deirdre Hennessy ,&nbsp;Niamh Harbourne ,&nbsp;Karina M. Pierce ,&nbsp;Emma L. Feeney ,&nbsp;Eileen R. Gibney","doi":"10.1016/j.jnutbio.2025.110004","DOIUrl":"10.1016/j.jnutbio.2025.110004","url":null,"abstract":"<div><div>Whole milk powder (WMP) produced from pasture-fed dairy herds has been shown to have increased concentrations of unsaturated fatty acids (FA), including, but not limited to, ALA (C18:3 n-3) and oleic acid (C18:1 <em>cis</em>-9), compared to WMP derived from indoor herds consuming total mixed ration (TMR). Dairy products have been shown to have neutral or beneficial effects on cardiometabolic health, however, evidence on WMP in this area is lacking. Given the global market for WMP as a food ingredient, an investigation into the effect of TMR-fed vs pasture-fed WMP on human health is warranted. Therefore, the aim of this study was to test the effect of WMP derived from TMR-fed and pasture-fed herds on circulating FA concentrations and other markers of cardiometabolic health in adults. Healthy subjects were randomized to receive up to 200 g WMP/day as part of a 6-week crossover trial, with a 4-week washout period. WMP was produced from milks of TMR-fed and pasture-fed cows. WMPs were isocaloric and macro-nutrient matched. The primary outcome was difference in circulating FA between weeks 0 and 6. Changes in cholesterol concentrations, glycemic control, blood pressure and anthropometry were secondary outcomes. Dietary intake was also analyzed. A total of <em>n</em> 29 participants, 58.6% male, with a mean±SE age of 39.8±2.3 years and BMI of 26.12±1.39 kg/m² completed the study protocol. No time × treatment interactions were observed for cholesterol concentrations, markers of glycemic control, blood pressure or anthropometry. There was no time × treatment interaction for classes of FA, however, the very long-chain saturated FA, lignoceric acid (C24:0), decreased in response to pasture-fed WMP consumption (−0.05±0.04 %TFA) with no change observed in response to the TMR WMP consumption (0.00±0.04 %TFA, <em>P</em>=.041), although this was not significant after Bonferroni correction for Type 2 error. Chronic, high-dose consumption of TMR and pasture-fed WMP had no effect on cardiometabolic health in healthy adults, despite different fatty acid composition. Comparison of foods with a proven dairy matrix effect, <em>e.g.</em>, cheese made from TMR-fed and pasture-fed milks, may have more promising effects on human health. This trial was registered as ISRCTN10490434 (<span><span>https://doi.org/10.1186/ISRCTN10490434</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"145 ","pages":"Article 110004"},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293964","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}