Journal of Nutritional Biochemistry最新文献

{"title":"Joint effect of hyperuricemia and severe vitamin D deficiency on all-cause and cardiovascular mortality among individuals with diabetes","authors":"Yingdong Han ,&nbsp;Tiange Xie ,&nbsp;Zhikai Li,&nbsp;Menghui Yao,&nbsp;He Zhao,&nbsp;Juan Wu,&nbsp;Yun Zhang,&nbsp;Xuejun Zeng","doi":"10.1016/j.jnutbio.2025.110083","DOIUrl":"10.1016/j.jnutbio.2025.110083","url":null,"abstract":"<div><div>This study aims to investigate the individual and joint associations of hyperuricemia (HUA) and severe Vitamin D deficiency (SVDD) on the all-cause and cardiovascular disease (CVD) mortality among patients with diabetes mellitus (DM) by analyzing data from the National Health and Nutrition Examination Survey (NHANES). Data of DM patients aged ≥20 years from the NHANES 2001-2018 were included in this study. Survey-weighted multivariable cox proportional hazards regression models, Kaplan–meier curve and restricted cubic spline analysis were employed to evaluate the individual and joint associations of HUA and SVDD with the all-cause and CVD mortality of DM patients. Sensitivity analyses, propensity score matching, and stratified analyses were performed to test the stability of our findings. Mediation analysis based on SIRI and HbA1c was also conducted. A total of 7,869 (Weighted <em>N</em>=27512325) patients with DM aged 20 and older were involved. The weighted mean (standard deviation (SD)) level of SUA and 25-hydroxyvitamin D (25(OH)D) were 5.74 (1.58) mg/dL and 62.51 (27.80) nmol/L, respectively. The mean follow-up time was 6.83±4.63 years, and 1,967 deaths were documented. The all-cause and CVD mortality rates per 1,000 person-year among DM patients were 28.30 and 9.49, respectively. After adjusting for confounding factors, patients with HUA and SVDD exhibited the higher risk of all-cause [HR: 1.28 (1.09–1.50) for HUA and 1.44 (1.07–1.94) for SVDD] and CVD [HR: 11.54 (1.01–2.36) for HUA and 1.98 (1.19–3.28) for SVDD] mortality. Kaplan–Meier curves demonstrated a statistically significant difference in survival probability over different HUA and SVDD categories among DM patients. The joint analysis revealed that HUA and SVDD have a joint effect on all-cause mortality (HR: 1.90 [1.23–2.93]) and CVD mortality (HR: 2.60 [1.45–4.65]) among patients with DM. Sensitivity analysis, propensity score matching and stratified analyses confirmed the stability of the research results. Mediation analyses further revealed that 11.4% of the SUA–mortality association was mediated through SIRI, and 1.96% of the 25(OH)D–mortality association through glycated hemoglobinA1c (HbA1c). HUA and SVDD comorbidity is significantly associated with elevated risk of all-cause and CVD mortality in DM patients. These findings indicate that concurrent management of HUA and SVDD may improve prognosis of DM patients.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110083"},"PeriodicalIF":4.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957968","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":"Resveratrol Improves Idiopathic Pulmonary Fibrosis by Targeting IKZF3.","authors":"Shuai Liu, Lixin Wang, Yinyan Yue, DongBo Ma, Xiang Deng, Yuanfang Wang, Dongdong Wu, Yang Wang, Qiuge Wu","doi":"10.1016/j.jnutbio.2025.110082","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110082","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited treatment options. This study investigates the therapeutic potential of resveratrol, a natural compound, in treating IPF by targeting IKZF3, a transcription factor upregulated in IPF patients. Using bioinformatics analysis of the GSE110147 dataset, we identified IKZF3 as a key molecule in IPF progression. In vitro experiments with bleomycin (BLM)-treated A549 cells showed that IKZF3 overexpression exacerbated cell death and fibrosis, while its silencing reversed these effects. Resveratrol treatment significantly improved cell viability, reduced fibrosis markers, and inhibited IKZF3's transcriptional regulation of IL-33, which in turn decreased ILC-2 activation. Molecular docking revealed a strong binding affinity between resveratrol and IKZF3. In vivo validation using a BLM-induced IPF mouse model demonstrated that resveratrol reduced lung fibrosis and downregulated fibrosis-related markers. Our findings suggest that targeting IKZF3 with resveratrol may offer a novel therapeutic strategy for IPF, highlighting the potential of this combination to improve disease outcomes.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110082"},"PeriodicalIF":4.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957937","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":"Role of immunity and inflammation in sarcopenic obesity","authors":"Yu-Cen Ma ,&nbsp;Xiao-Ping Li ,&nbsp;Xiao-Ye Lin ,&nbsp;Ke-Xin Zhang ,&nbsp;Ji-Yan Leng","doi":"10.1016/j.jnutbio.2025.110077","DOIUrl":"10.1016/j.jnutbio.2025.110077","url":null,"abstract":"<div><div>The global aging population brings about various age-related clinical concerns, including sarcopenic obesity (SO), which poses a significant health risk for older individuals. SO is characterized by the coexistence of two phenotypes, namely, sarcopenia and obesity, and its pathogenesis is multifaceted. Current research indicates that both reduced muscle mass and excessive fat accumulation are associated with chronic low-grade inflammatory conditions. In addition, these two issues have the potential to exacerbate each other's effects. This review highlights recent advances in understanding the role of immunity and inflammation in the development of SO. Specifically, we provide a novel perspective by integrating how aging and obesity jointly contribute to SO through immune-inflammatory pathways. Furthermore, we discuss the influence of sex differences in immune responses and inflammatory processes, which may account for the variability observed in SO susceptibility and progression. Finally, we summarize current and emerging therapeutic strategies to provide potential directions for the treatment of SO.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110077"},"PeriodicalIF":4.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957927","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":"Inhibition of glucagon secretion from pancreatic α-cells by the bile acid TUDCA involves a S1PR2-PI3K pathway","authors":"Joel Alves da Silva Junior ,&nbsp;Jean Franciesco Vettorazzi ,&nbsp;Sergi Soriano ,&nbsp;Eva Bru-Tari ,&nbsp;Talía Boronat-Belda ,&nbsp;Manuel Castellano-Muñoz ,&nbsp;Patrícia Cristine Borck ,&nbsp;Rosane Aparecida Ribeiro ,&nbsp;Gabriela Moreira Soares ,&nbsp;Camila Lubaczeuski ,&nbsp;Antônio Carlos Boschero ,&nbsp;Laura Marroqui ,&nbsp;Ángel Nadal ,&nbsp;Paloma Alonso-Magdalena ,&nbsp;Ivan Quesada ,&nbsp;Everardo Magalhães Carneiro","doi":"10.1016/j.jnutbio.2025.110076","DOIUrl":"10.1016/j.jnutbio.2025.110076","url":null,"abstract":"<div><div>The global prevalence of type 2 diabetes (T2D) continues to rise, and predictions indicate alarming records in coming decades. Although pancreatic β-cell dysfunction and insulin resistance are key factors in the etiology of T2D, the impairment of α-cells has been also implicated. Hyperglucagonemia and altered suppression of glucagon release can be frequently found in individuals with T2D, contributing to hyperglycemia. Bile acids have emerged as novel signaling molecules that regulate metabolism. A wealth of evidence shows that oral treatment with the bile acid TUDCA has therapeutic benefits in T2D, primarily by improving both insulin release from β-cells and insulin sensitivity in peripheral tissues. However, it is unknown whether TUDCA could affect other processes involved in the control of glucose metabolism. Here, we show that acute administration of TUDCA exerts a glucagonstatic action on mouse pancreatic islets and glucagon-releasing αTC1-9 cells. Pharmacological and/or molecular inhibition of the sphingosine-1-phosphate receptor 2 (S1PR2) and the PI3K pathway blunted the TUDCA effect on glucagon release. Additionally, TUDCA increased the activity of ATP-sensitive <em>K</em>⁺ (K_ATP) channels, decreased action currents and inhibited Ca²⁺ signaling in α-cells without directly affecting the exocytotic process. Glucose-induced suppression of glucagon secretion was found to be compromised under hyperglycemic conditions, yet TUDCA was able to inhibit α-cell function, highlighting its glucagonstatic effect in a pathological context. Collectively, these findings suggest that TUDCA-induced inhibition of glucagon secretion involves the opening of α-cell K_ATP channels and activation of the S1PR2/PI3K pathway, expanding the repertoire of potential therapeutic benefits of TUDCA in diabetes treatment.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110076"},"PeriodicalIF":4.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957948","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 prevents ethanol-induced reward behavior in adolescent rats through inhibition of TRPM3-dependent inflammation in the pVTA","authors":"Sanjay N. Awathale,&nbsp;Kamini R. Shirasath,&nbsp;Balaji R. More,&nbsp;Gajendra N. Pardeshi,&nbsp;Sameer N. Goyal,&nbsp;Kartik T. Nakhate","doi":"10.1016/j.jnutbio.2025.110078","DOIUrl":"10.1016/j.jnutbio.2025.110078","url":null,"abstract":"<div><div>Ethanol intake activates the posterior ventral tegmental area (pVTA), enhancing dopamine synthesis in the nucleus accumbens shell (AcbSh) and contributing to Alcohol Use Disorder (AUD). Chronic adolescent ethanol exposure promotes neuroinflammation and disrupts reward pathways, increasing susceptibility to addiction. Although transient receptor potential melastatin 3 (TRPM3) activation promotes inflammation and contributes to psychiatric disorders, its role in reward mechanisms remains unclear. Current AUD treatments reduce cravings and promote alcohol aversion but are often limited by adverse effects, highlighting the need for safer, natural alternatives. Naringenin, a citrus flavonoid, exhibits anti-inflammatory and neuroprotective properties. This study investigates the involvement of TRPM3 in reward processing and whether naringenin modulates its activity to reduce ethanol-induced neuroinflammation and craving. The effect of intraperitoneal (i.p.) naringenin (50 mg/kg) was tested by administering it daily prior to ethanol (2 g/kg, 20% w/v, i.p.) in adolescent male Sprague-Dawley rats for 2 weeks. Reward behavior was assessed using the conditioned place preference and open field tests. The pVTA was examined for TRPM3 expression, biochemical and synaptic changes, while dopamine levels in the AcbSh. Ethanol increases preference scores (0.46±0.01), locomotion (84.4±2.13), TRPM3 expression (48.77±2.58%) and co-expression with tyrosine hydroxylase (27.70±1.29%), TNF-α (298.29±10.48 pg/mg protein) and IL-6 (198.29±9.31 pg/mg protein), dendritic length in the pVTA (887.31±21.07 µm), and dopamine contents in the AcbSh (387,126.1±10,390.04 AUC). Naringenin reversed these effects, suggesting its potential anti-addictive properties and supporting TRPM3 as a promising therapeutic target for AUD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110078"},"PeriodicalIF":4.9,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873647","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":"Ketogenic diet influences the renin-angiotensin-aldosterone system components in the healthy and inflamed intestine of male mice","authors":"Hanna Launonen ,&nbsp;Lotta Toivio ,&nbsp;Jere Lindén ,&nbsp;Hanne Salmenkari ,&nbsp;Riitta Korpela","doi":"10.1016/j.jnutbio.2025.110079","DOIUrl":"10.1016/j.jnutbio.2025.110079","url":null,"abstract":"<div><div>Inhibiting the overexpression of the renin-angiotensin-aldosterone system (RAAS) alleviates intestinal inflammation. Recently, we and others reported that a high-fat, low carbohydrate, ketogenic diet (KD), shown to downregulate the conventional RAAS components in rat lung and adipose tissue, can protect mice from experimental colitis. Here we assessed whether the proinflammatory angiotensin-converting enzyme - angiotensin receptor type 1 (ACE-AT1R) axis and the anti-inflammatory angiotensin-converting enzyme 2- MAS1 receptor (ACE2-MAS1) axis RAAS components are influenced by the consumption of a KD rich either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) in healthy and inflamed intestine of C57BL/6 J male mice. In healthy jejunum, KD increased the AT2R protein level and decreased <em>Ace2</em> level regardless of the fat source, whereas in the healthy colon, the RAAS components were unaffected by the dietary interventions. In colon, administration of 2.5% (w/v) dextran sodium sulfate (DSS) for 5 days upregulated ACE protein while downregulating <em>Agtr2</em> gene expression. These DSS-induced changes were absent in both KD groups. Furthermore, the DSS-SFA-KD group exhibited lower <em>angiotensinogen</em> gene expression than the DSS animals. Additionally, LA-KD mitigated the DSS-induced decrease in <em>Ace2</em> gene expression. In conclusion, intestinal RAAS component expression is influenced by KDs, and the DSS-induced upregulation of proinflammatory RAAS components were not observed in DSS-KD groups.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110079"},"PeriodicalIF":4.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873646","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":"Berberine alleviates metabolic dysfunction-associated steatohepatitis by enhancing the abundance of Akkermansia muciniphila","authors":"Jiahui Xu ,&nbsp;Yueqiong Lao ,&nbsp;Wendi Zhang ,&nbsp;Lincao Chen ,&nbsp;Hao Zhang ,&nbsp;Hongbin Liu ,&nbsp;Ting Yan ,&nbsp;Ruo Huang ,&nbsp;Yangzhi Xu ,&nbsp;Liangying Ye ,&nbsp;Fachao Zhi ,&nbsp;Hui Yang","doi":"10.1016/j.jnutbio.2025.110069","DOIUrl":"10.1016/j.jnutbio.2025.110069","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatohepatitis (MASH) is associated with intestinal barrier defects and gut microbiota dysbiosis. The gut commensal bacterium <em>Akkermansia muciniphila</em> (Akk) maintains intestinal barrier integrity and improves MASH-related metabolic syndromes. Berberine (BBR), a traditional Chinese medicine, shows promise in treating MASH. However, research on drugs that target Akk regulation and its underlying mechanisms remains limited. This study investigates the mechanisms by which BBR regulates Akk in MASH. We fed C57BL/6 J male mice a methionine-choline-deficient (MCD) diet for 6 weeks to establish the MASH mouse models. The gut microbiota was analyzed using 16S rRNA sequencing and bacterial quantification measured by qPCR analysis. An antibiotic cocktail (Abx) and fecal microbiota transplantation (FMT) were applied to modulate gut microbiota. Results showed that BBR reduced hepatic and colonic inflammation, preserved intestinal barrier integrity and prevented microbiota translocation into the liver. The 16S rRNA sequencing and qPCR analysis revealed a significant increase in Akk abundance in fecal samples following BBR treatment. Mechanistically, BBR did not promote Akk growth directly, but it reduced the bacterial load and enhanced MUC2 expression, thereby facilitating Akk colonization indirectly. While disruption of the gut microbiota by antibiotics treatment weakened the therapeutic effect of berberine on MASH, transplanting of the fecal microbiota from BBR-treated mice could mitigate MASH in antibiotic-treated mice. Finally, BBR and Akk exhibited synergistic therapeutic effects against MASH. Our study illustrated that BBR alleviates MASH mice by enhancing Akk abundance and restoring intestinal barrier integrity. BBR and Akk combination therapy would be a promising strategy for MASH prevention.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110069"},"PeriodicalIF":4.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859318","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/SIRT1/GPX4 signaling pathway mediates the protective effect of puerarin against LPS-induced endometritis in mice","authors":"Ke Wang ,&nbsp;Lifu Cai ,&nbsp;Jianguo Sun ,&nbsp;Li Liu ,&nbsp;Shouyang Gao","doi":"10.1016/j.jnutbio.2025.110072","DOIUrl":"10.1016/j.jnutbio.2025.110072","url":null,"abstract":"<div><div>Endometritis is a chronic inflammation characterized by plasma cell infiltration into the endometrial stroma, which can lead to adverse pregnancy outcomes such as infertility, recurrent miscarriages, and repeated embryo transfer failures. Puerarin (PR) is a flavonoid derivative that has anti-inflammatory and antibacterial effects. The aim of this study is to evaluate the effects of PR on LPS-induced endometritis and to elucidate its mechanism. The changes of inflammatory factors in endometrial tissue were detected by ELISA. Western-blot technology was used to analyze the expression of AMPK/SIRT1/GPX4 signaling at the protein level. It was found that PR markedly alleviated LPS-induced uterine pathological injury and the degree of inflammation. PR also inhibited LPS-induced ferroptosis in uterine tissues. In further mechanistic studies, the data showed that PR significantly inhibited LPS-induced NF-κB activation. Meanwhile, PR could up-regulate the expression of AMPK, SIRT1, and GPX4 decreased by LPS. In vitro, PR significantly inhibited LPS-induced TNF-α and IL-lβ expression in mouse endometrial epithelial cells (MEECs). The inhibition of PR on LPS-induced inflammatory response were reversed by AMPK inhibitor compound C and SIRT1 inhibitor EX-527. In conclusion, the data demonstrated that PR exhibited therapeutic effects against LPS-induced endometritis through attenuating ferroptosis and inflammatory response.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110072"},"PeriodicalIF":4.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859317","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":"Association between polygenic risk scores and vitamin D status among Chinese healthy infants and toddlers: The role of dietary intake and supplementation practice","authors":"Keith T.S. Tung ,&nbsp;Maxine Poon ,&nbsp;Hing Wai Tsang ,&nbsp;Joanna Y.L. Tung ,&nbsp;Rosa S. Wong ,&nbsp;Jason C.S. Yam ,&nbsp;Ian C.K. Wong ,&nbsp;Patrick Ip","doi":"10.1016/j.jnutbio.2025.110070","DOIUrl":"10.1016/j.jnutbio.2025.110070","url":null,"abstract":"<div><div>Hypovitaminosis D during infancy may adversely affect health and developmental outcomes in early childhood. Our study aims to explore the individual and combined effects of the eight selected genetic variants (rs4588, rs7041, rs2282679, rs2228570, rs1993116, rs4646536, rs11234027, and rs10783219) on vitamin D status among infants and toddlers with sufficient and insufficient vitamin D intake. A multi-centre cross-sectional study was conducted to recruit 616 infants and toddlers aged 7–23 months. A polygenic risk score (PRS) was computed from eight selected genetic variants. Questionnaire on family demographics, dietary intake and the use of vitamin D containing supplements were completed by parents. Participants’ vitamin D status was classified based on their serum 25(OH)D concentrations measured by Liquid Chromatography Tandem Mass Spectrometry. Analyses showed that rs7041T, rs4588A, and rs2282679C carriers had significantly lower serum 25(OH)D concentration. Participants were categorized by their PRS (Low: 1–4; Low Medium: 5–6; High Medium: 7–8; and High: 9–13), in which low risk group had significantly higher serum 25(OH)D concentration than other three groups (<em>P</em>&lt;.05). Effect of PRS on vitamin D concentrations was mainly observed in participants with insufficient vitamin D intake and those not using vitamin D containing supplements (<em>P</em>&lt;.05). Our study revealed the individual and combined effects of genetic variants on serum vitamin D concentrations. Sufficient vitamin D intake and the use of vitamin D containing supplements can help reduce the effect of genetic risk and should be emphasized in guidelines for the prevention of hypovitaminosis D in infants and toddlers.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110070"},"PeriodicalIF":4.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855584","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":"Lysine β-hydroxybutyrylation in metabolic plasticity and disease pathogenesis","authors":"Kailing Hu ,&nbsp;Jiayi Xu ,&nbsp;Xinyan Li ,&nbsp;Liangwen Yan ,&nbsp;Shenkang Tang ,&nbsp;Gang Wang ,&nbsp;Ying Guo ,&nbsp;Pengfei Liu","doi":"10.1016/j.jnutbio.2025.110074","DOIUrl":"10.1016/j.jnutbio.2025.110074","url":null,"abstract":"<div><div>Lysine β-hydroxybutyrylation (Kbhb) represents a novel post-translational modification (PTM) mediated by ketone body metabolites, particularly β-hydroxybutyric acid (BHB). This modification exhibits dynamic elevation under ketogenic conditions including diabetic ketoacidosis, neonatal metabolic disorders, fasting, and sustained physical exertion, where circulating BHB concentrations exceed physiological thresholds. Emerging evidence positions Kbhb as a critical epigenetic-metabolic interface, with demonstrated regulatory roles spanning oncology, immunomodulation, cardiovascular homeostasis, neuropsychiatric disorders, circadian biology, and developmental processes. Mechanistically, Kbhb affects metabolic plasticity through modulating structural modification of key metabolic enzyme as well as metabolic flux. In addition, Kbhb exerts pleiotropic effects via competitive interplay with canonical PTMs (acetylation, methylation) at critical lysine residues. Kbhb-induced epigenomic reorganization through enhancer/promoter domain enrichment facilitates transcriptional activation of functional gene and mediates transcriptional network during the progression of multiple diseases. This review systematically examines the discovery timeline, enzymatic machinery governing Kbhb dynamics (writers/erasers/readers), molecular mechanisms underlying its pathophysiological functions, and therapeutic implications across disease states. The elucidation of Kbhb-induced metabolic signaling paradigms and other molecular interfaces catalyzes the development of innovative therapeutic strategies across multiple diseases.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110074"},"PeriodicalIF":4.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855540","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}