Journal of Nutritional Biochemistry最新文献_第5页

Metabolomics identifies riboflavin as a therapeutic agent for acute pancreatitis 代谢组学鉴定核黄素作为急性胰腺炎的治疗剂。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-04 DOI: 10.1016/j.jnutbio.2025.110225

Yuxin Shi , Jie Peng

Acute pancreatitis (AP) is a self-limiting inflammatory disorder, but severe cases can lead to persistent organ failure with high mortality. Metabolic dysregulation and inflammatory activation play critical roles in AP pathogenesis, highlighting the metabolic-inflammation crosstalk as a potential therapeutic target. Although riboflavin, an essential water-soluble vitamin, has been implicated in modulating disease processes, its role in AP remains unclear. In this study, untargeted metabolomics identified significant riboflavin downregulation in an AP mouse model. Subsequent in vivo experiments demonstrated that riboflavin intervention (25, 50, and 100 mg/kg) ameliorated pancreatic injury and systemic inflammation, with 50 mg/kg exhibiting optimal efficacy. Targeted metabolomics revealed elevated acetate levels following riboflavin supplementation. At the same time, transcriptomic and molecular biology assays showed riboflavin-mediated downregulation of HDAC3, a key acetate downstream target, and suppression of NF-κB pathway activation. In vitro, riboflavin and acetate mitigated pancreatic acinar cell damage, including apoptosis and necrosis, and inhibited NF-κB signaling. Rescue experiments using the HDAC3 inhibitor RGFP966 further provided pharmacological evidence for a mechanistic link between the acetate-HDAC3 axis and riboflavin’s protective effects. Collectively, these findings reveal that riboflavin alleviates AP, and its effect is associated with the modulation of the acetate-HDAC3 axis, offering a novel therapeutic strategy for this condition.

急性胰腺炎（AP）是一种自限性炎症性疾病，但严重的病例可导致持续的器官衰竭，死亡率高。代谢失调和炎症激活在AP发病机制中起关键作用，强调代谢-炎症串扰是潜在的治疗靶点。尽管核黄素（一种必需的水溶性维生素）与调节疾病过程有关，但其在AP中的作用仍不清楚。在这项研究中，非靶向代谢组学在AP小鼠模型中发现了显著的核黄素下调。随后的体内实验表明，核黄素干预（25、50和100 mg/kg）可改善胰腺损伤和全身性炎症，其中50 mg/kg的效果最佳。靶向代谢组学显示，补充核黄素后，乙酸水平升高。同时，转录组学和分子生物学分析显示，核黄素介导的HDAC3（醋酸盐下游关键靶点）下调，并抑制NF-κB通路的激活。核黄素和醋酸酯可减轻胰腺腺泡细胞凋亡、坏死等损伤，抑制NF-κB信号传导。利用HDAC3抑制剂RGFP966进行的救援实验进一步为醋酸酯-HDAC3轴与核黄素的保护作用之间的机制联系提供了药理学证据。总的来说，这些发现表明核黄素缓解AP，其作用与醋酸酯- hdac3轴的调节有关，为这种疾病提供了一种新的治疗策略。

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引用次数: 0

Pre-but not post-natal nutritional restriction promotes mammary development 产前而非产后营养限制促进乳房发育。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-04 DOI: 10.1016/j.jnutbio.2025.110226

Xusheng Dong, Qiuling Hou, Yingyu Mu, Xueyan Lin, Zhiyong Hu, Yun Wang, Yizhao Shen, Zhonghua Wang

The mammary gland undergoes continuous growth, differentiation, and cyclical remodeling throughout the whole life, with morphogenesis from the embryonic stage to adulthood being crucial and highly sensitive to nutritional supply. While moderate nutritional restriction in early life and subsequent restore can promote the tissues development such as muscle, its effects on the mammary remain largely unexplored and appear to depend critically on the development stage. Thus, the effects of moderated nutritional restriction in early life including embryonic (ER), suckling (SR), or pubertal (PR) periods on mammary development and subsequent lactation performance in mice were investigated in the present study. In this study, we imposed nutritional restriction on mice during either a single period or two periods. Mammary gland and serum samples were collected at maturity (56 d) and on lactation day 15 for hormonal, histological, and transcriptomic analyses. Our results demonstrate that ER enhances mammary development and adult lactation capacity by boosting proliferative activity and increasing the mammary stem cell content. In contrast, postnatal nutritional restrictions (SR and PR) disrupt normal gland morphogenesis by attenuating hormonal signaling responses and reducing stromal tissue remodeling. Notably, the adverse effects of SR on mammary morphology are reversible upon nutritional repletion, with no subsequent impact on milk production, whereas PR leads to a significant impairment in adult lactation. These findings reveal distinct regulatory mechanisms of nutritional intervention at various development stages and provide a foundational basis for optimizing lactational outcomes through targeted nutritional strategies.

乳腺在一生中经历着持续的生长、分化和周期性的重塑，其中从胚胎期到成年期的形态发生至关重要，对营养供应高度敏感。虽然生命早期适度的营养限制和随后的恢复可以促进肌肉等组织的发育，但其对乳房的影响在很大程度上仍未被探索，似乎主要取决于发育阶段。因此，本研究探讨了生命早期包括胚胎期（ER）、哺乳期（SR）或发育期（PR）的适度营养限制对小鼠乳腺发育和随后的泌乳性能的影响。在这项研究中，我们在一段时间或两段时间内对小鼠进行营养限制。在成熟（56天）和哺乳第15天采集乳腺和血清样本，进行激素、组织学和转录组学分析。我们的研究结果表明，内质网通过促进增殖活性和增加乳腺干细胞含量来促进乳腺发育和成人泌乳能力。相反，产后营养限制（SR和PR）通过减弱激素信号反应和减少基质组织重塑来破坏正常的腺体形态发生。值得注意的是，SR对乳腺形态的不良影响在营养补充后是可逆的，不会对产奶量产生后续影响，而PR会对成人泌乳产生重大损害。这些发现揭示了不同发育阶段营养干预的不同调控机制，并为通过有针对性的营养策略优化哺乳结果提供了基础依据。

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引用次数: 0

Dietary fiber-derived butyrate ameliorates pulmonary fibrosis by inhibiting YBX1 ubiquitination 膳食纤维来源的丁酸盐通过抑制YBX1泛素化改善肺纤维化。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-02 DOI: 10.1016/j.jnutbio.2025.110210

Mengyu Li , Tianyu Pan , Xiaoli Ma , Xiaofang Hu , Ji Jiang , Yafei Zhang , Lei Zhang , Xin Pan , Yuanyuan Wang

Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease characterized by aberrant epithelial-mesenchymal transition (EMT) and extracellular matrix deposition. Dietary fiber, fermented by gut microbiota into butyrate, exerts anti-fibrotic effects, yet the underlying mechanisms are not fully elucidated. YBX1 plays a crucial role in the regulation of fibrosis and EMT. However, its function in PF remains unclear. This study aims to investigate the role of dietary fiber in PF and whether YBX1 mediates the anti-fibrotic effect of butyrate in PF. The roles of the high fiber (HF) diet and butyrate in PF and the changes in butyrate content were evaluated using RT-qPCR, Western blotting, immunofluorescence (IF) and GC-MS. RNA sequencing was used to analyze the downstream action sites of butyrate. The function of YBX1 in PF was elucidated through overexpression of YBX1, RNA sequencing, and KEGG pathway analysis. The interaction between YBX1 and butyrate was examined using ubiquitination and CHX assays. The results showed that the HF diet increased butyrate levels, thereby ameliorating PF by inhibiting EMT. The expression of YBX1 was downregulated in PF and overexpression of YBX1 inhibited EMT by regulating CYP1A1/NF-κB signaling pathway, thereby improving the progression of PF. Butyrate upregulated YBX1 protein expression by reducing its ubiquitination. This work provides new insights and promising strategies for the prevention and treatment of PF through dietary interventions.

肺纤维化（PF）是一种进行性和致死性间质性肺疾病，其特征是异常的上皮-间质转化（EMT）和细胞外基质沉积。膳食纤维经肠道菌群发酵生成丁酸盐，具有抗纤维化作用，但其作用机制尚未完全阐明。YBX1在纤维化和EMT的调控中起着至关重要的作用。然而，其在PF中的作用尚不清楚。本研究旨在探讨膳食纤维在PF中的作用以及YBX1是否介导了丁酸盐在PF中的抗纤维化作用，采用RT-qPCR、Western blotting、免疫荧光（IF）和GC-MS等方法评价高纤维饲料和丁酸盐在PF中的作用以及丁酸盐含量的变化。利用RNA测序技术分析丁酸酯的下游作用位点。通过YBX1过表达、RNA测序和KEGG通路分析，阐明了YBX1在PF中的功能。通过泛素化和CHX检测YBX1与丁酸盐的相互作用。结果表明，HF饲粮通过抑制EMT，提高了丁酸盐水平，从而改善了PF。YBX1在PF中表达下调，YBX1过表达通过调节CYP1A1 / NF-κB信号通路抑制EMT，从而改善PF的进展，丁酸盐通过降低YBX1的泛素化而上调其表达。这项工作为通过饮食干预预防和治疗PF提供了新的见解和有希望的策略。

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引用次数: 0

Astaxanthin alleviates DSS-induced ulcerative colitis in mice associated with Nrf2-mediated ferroptosis independently of gut microbiota modulation 虾青素可减轻与nrf2介导的铁下垂相关的小鼠dss诱导的溃疡性结肠炎，而不依赖于肠道菌群调节。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-01 DOI: 10.1016/j.jnutbio.2025.110212

Meng-Xuan Wei , Xin-Yi Wu , Jia-Wei Lin , Jia-Yu Huang , Jie Cheng , Wei-Feng Huang , Guang-Hui Xu , Li-Tao Yi

Astaxanthin, a natural carotenoid predominantly synthesized by marine microorganisms, has shown promise in attenuating inflammatory diseases, yet its role in colitis remains unclear. Here, we evaluated the therapeutic effects of astaxanthin in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. Our findings revealed that astaxanthin significantly ameliorated colitis symptoms, notably at the dose of 100 mg/kg, demonstrated by reduced Disease Activity Index (DAI), increased colon length, diminished colon histopathological damage, and enhanced goblet cell population. Mechanistically, astaxanthin decreased proinflammatory cytokines and malondialdehyde (MDA) levels, suppressed Keap1 expression, activated phosphorylated Nuclear factor erythroid 2-related factor two (Nrf2), and increased downstream protein expression of HO-1 and GPX4, ultimately inhibiting ferroptosis. Although astaxanthin altered gut microbiota composition, antibiotic treatment and fecal microbiota transplantation confirmed that its anti-colitis effects were independent of microbiota changes. These findings suggest that astaxanthin alleviates colitis associated with Nrf2 pathway mediated ferroptosis, rather than through gut microbiota modulation.

虾青素是一种主要由海洋微生物合成的天然类胡萝卜素，已显示出减轻炎症性疾病的希望，但其在结肠炎中的作用尚不清楚。在这里，我们评估虾青素对葡聚糖硫酸钠（DSS）诱导的小鼠溃疡性结肠炎的治疗作用。我们的研究结果显示，虾青素显著改善结肠炎症状，特别是在100 mg/kg的剂量下，表现为降低疾病活动指数（DAI），增加结肠长度，减少结肠组织病理学损伤，增加杯状细胞群。机制上，虾青素降低促炎细胞因子和丙二醛（MDA）水平，抑制Keap1表达，激活磷酸化核因子红系2相关因子2 (Nrf2)，增加下游HO-1和GPX4蛋白表达，最终抑制铁凋亡。虽然虾青素改变了肠道菌群组成，但抗生素治疗和粪便菌群移植证实其抗结肠炎作用与菌群变化无关。这些发现表明虾青素缓解与Nrf2途径介导的铁下垂相关的结肠炎，而不是通过肠道菌群调节。

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引用次数: 0

Kaempferol stimulates dermal papilla cells and upregulates Wnt/β-catenin signaling pathway for androgenetic alopecia treatment 山奈酚刺激真皮乳头细胞和上调Wnt/β-catenin信号通路治疗雄激素性脱发。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-01 DOI: 10.1016/j.jnutbio.2025.110214

Changjiang Zhao , Lingling Jia , Ruiyu Luo , He Yan , Zihan Li , Hua Jiang , Yufei Li

Androgenetic alopecia (AGA) is the most common form of progressive hair loss, marked by a multifaceted pathogenesis and a lack of effective pharmacological treatments to arrest its progression. Flavonoids have drawn considerable research attention for their potential in fostering hair regeneration, yet kaempferol (Kae), a well-researched flavone, remains unexplored as a therapeutic agent for AGA. This study delves into the mechanisms and efficacy of Kae in AGA treatment, employing a blend of in vivo and in vitro experiments, complemented by transcriptome sequencing and molecular docking techniques. In vitro, Kae exhibited no significant toxicity to dermal papilla cells (DPCs); instead, it enhanced DPCs proliferation and migration in a dose-dependent manner, and significantly mitigated dihydrotestosterone (DHT)-induced cellular damage. Transcriptomic analysis and RT-qPCR indicated that Kae modulates the Wnt/β-catenin signaling pathway. Molecular docking studies indicated that Kae has binding potential to β-catenin and Cyclin D1, pivotal proteins within this pathway. Subsequent immunofluorescence experiments and Western blot confirmed Kae’s ability to promote β-catenin nuclear translocation and inhibit DHT-induced downregulation of β-catenin and Cyclin D1. In vivo, oral Kae administration substantially promoted hair regeneration in an AGA mouse model, with efficacy on par with oral finasteride. In conclusion, this study presents robust evidence that Kae effectively stimulates hair growth by bolstering DPCs function and counteracting DHT-induced damage, thus holding promising therapeutic potential for AGA sufferers.

雄激素性脱发（AGA）是最常见的进行性脱发形式，其特点是多方面的发病机制和缺乏有效的药物治疗来阻止其进展。黄酮类化合物因其促进头发再生的潜力而引起了相当大的研究关注，然而山奈酚（Kae），一种研究得很好的黄酮类化合物，作为AGA的治疗剂仍未被开发。本研究采用体内和体外实验相结合的方法，辅以转录组测序和分子对接技术，深入研究了Kae治疗AGA的机制和疗效。在体外，Kae对真皮乳头细胞（DPCs）无明显毒性；相反，它以剂量依赖的方式增强了DPCs的增殖和迁移，并显著减轻了双氢睾酮（DHT）诱导的细胞损伤。转录组学分析和RT-qPCR表明，Kae调控Wnt/β-catenin信号通路。分子对接研究表明，Kae与该通路中的关键蛋白β-catenin和Cyclin D1具有结合潜力。随后的免疫荧光实验和Western blot证实Kae能够促进β-catenin核易位，抑制dht诱导的β-catenin和Cyclin D1的下调。在体内，口服Kae可显著促进AGA小鼠模型的毛发再生，其疗效与口服非那雄胺相当。总之，本研究提供了强有力的证据，证明Kae通过增强DPCs功能和抵消dht引起的损伤有效地刺激头发生长，因此对AGA患者具有良好的治疗潜力。

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引用次数: 0

Type 3 resistant starch from Canna edulis improves Parkinson's symptoms, including behavioral function and nerve damage, in Parkinson's model rats by regulating the gut-brain axis. 美人蕉中的3型抗性淀粉通过调节肠脑轴改善帕金森模型大鼠的行为功能和神经损伤等帕金森症状。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-01 DOI: 10.1016/j.jnutbio.2025.110191

Nan Zhang, Fangyuan Zhao, Tingting Miao, Nan Wang, Jiahui Wu, Shuting Tan, Xiang Wang, Xier Lihou, Yan Li, Yang Li, Feng Ou, Maochun Xiao, Aji Li, Rongting Min, Shiyao Su, Xueyong Wang

Intestinal microorganisms affect the pathogenesis of Parkinson's disease (PD) and, therefore, are a new research focus of PD treatment. Type 3 resistant starch from Canna edulis (Ce-RS3) regulates gut microbes and has prebiotic properties. The effects include decreased blood lipids, weight, and inflammation, as well as increased glycolipid metabolism. There are few reports on the use of prebiotics alone in the treatment of Parkinson's. In this study, based on the gut-brain axis, the pharmacological effects and related mechanisms of Ce-RS3 on PD were studied by analyzing intestinal bacteria and brain transcriptomics. Ce-RS3 improved motor function in PD model rats over a defined period and repaired PD-induced inflammation-related organ and neural damage. In addition, Ce-RS3 increased the number of short-chain fatty acid-producing, and other beneficial, bacteria. Transcriptomics showed that Ce-RS3 decreased inflammatory gene expression, upregulated the expression of the protein homeostasis-related gene Hspb1 and downregulated the expression levels of the protein aggregation-related genes Hdac6 and Ubd. Therefore, we hypothesized that Ce-RS3 plays a role in the treatment of PD by regulating the α-synuclein-related pathway through the brain-gut axis and protecting the neural tissues. This study provides a new intervention plan for the prevention and treatment of PD.

肠道微生物影响帕金森病（PD）的发病机制，是帕金森病治疗的新研究热点。美人蕉3型抗性淀粉（Ce-RS3）调节肠道微生物，具有益生元特性。其影响包括降低血脂、体重和炎症，以及增加糖脂代谢。关于单独使用益生元治疗帕金森氏症的报道很少。本研究以肠脑轴为基础，通过肠道细菌和脑转录组学分析，研究Ce-RS3对PD的药理作用及相关机制。Ce-RS3在一定时间内改善PD模型大鼠的运动功能，修复PD诱导的炎症相关器官和神经损伤。此外，Ce-RS3增加了短链脂肪酸产生菌和其他有益菌的数量。转录组学显示，Ce-RS3降低炎症基因表达，上调蛋白稳态相关基因Hspb1的表达，下调蛋白聚集相关基因Hdac6和Ubd的表达水平。因此，我们假设Ce-RS3通过脑肠轴调节α-突触核蛋白相关通路，保护神经组织，从而在PD的治疗中发挥作用。本研究为PD的防治提供了一种新的干预方案。

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引用次数: 0

Geniposidic acid from ginger-processed Eucommiae Cortex alleviates rheumatoid arthritis by modulating macrophage lactylation induced by exosomes from inflammatory fibroblast-like synoviocytes 姜杜仲皮质的Geniposidic酸通过调节炎性成纤维细胞样滑膜细胞外泌体诱导的巨噬细胞乳酸化来缓解类风湿关节炎。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-30 DOI: 10.1016/j.jnutbio.2025.110213

Yijing Pan , Chenxi Deng , Xinyue Liu , Shunshun Wang , Lin Chen , Anzheng Li , Jinsong Shu , Kang Xu , Xiong Ku , Chunli Wang

Eucommiae Cortex (EC), a Traditional Chinese health food product, is known for its anti-inflammatory, antioxidant, and hepatoprotective effects, with promising potential in treating rheumatoid arthritis (RA). This study used liquid chromatography-tandem mass spectrometry (LC-MS) to profile the bioactive compounds of ginger-processed EC (G-EC), focusing on its absorbed constituents and metabolic fate in vivo. Network pharmacology identified geniposidic acid (GPA) as a key bioavailable compound in G-EC, potentially alleviating RA. In vivo, GPA significantly improved RA symptoms. Additionally, exosomes from inflammatory fibroblast-like synoviocytes (FLSs) (LPS-exo) promoted M1 macrophage polarization, glycolytic activation, and synovial inflammation. GPA inhibited glycolysis, reduced M1 polarization induced by LPS-exo, and downregulated H3K56la histone lactylation. Mechanistic analysis suggested these effects involve the regulation of ATP-citrate lyase (ACLY) and Histone deacetylase 6 (HDAC6) expression. This study supports the therapeutic potential of GPA in RA and provides a foundation for further clinical research.

杜仲皮质（EC）是一种传统的中国保健食品，以其抗炎、抗氧化和保护肝脏的作用而闻名，在治疗类风湿性关节炎（RA）方面具有很大的潜力。本研究采用液相色谱-串联质谱法（LC-MS）分析生姜加工EC （G-EC）的生物活性成分，重点研究其在体内的吸收成分和代谢命运。网络药理学发现，geniposidic acid （GPA）是G-EC中关键的生物利用化合物，可能缓解RA。在体内，GPA显著改善RA症状。此外，炎性成纤维细胞样滑膜细胞（FLSs）（LPS-exo）外泌体促进M1巨噬细胞极化、糖酵解激活和滑膜炎症。GPA抑制糖酵解，降低LPS-exo诱导的M1极化，下调H3K56la组蛋白乳酸化。机制分析表明，这些作用与调节atp -柠檬酸裂解酶（ACLY）和组蛋白去乙酰化酶6 （HDAC6）的表达有关。本研究支持了GPA在RA中的治疗潜力，并为进一步的临床研究提供了基础。

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引用次数: 0

Betaine supplementation attenuates high-Se induced insulin resistance in C57BL/6 mice 补充甜菜碱可减轻高硒诱导的C57BL/6小鼠胰岛素抵抗。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-29 DOI: 10.1016/j.jnutbio.2025.110205

Jianrong Wang , Xue Zhang , Qin Wang , Feng Han , Xuesong Xiang , Jiaqiang Huang , Cuilan Fang , Yiqun Liu , Zhenwu Huang

Our previous research demonstrated that exogenous serine ameliorates insulin resistance in C57BL/6 mice fed a diet containing 0.8 mg/kg selenium, likely by serving as a methyl donor for SAM biosynthesis. This study aims to investigate whether betaine, an alternative methyl donor, can similarly mitigate high Se-induced IR in mice. Thirty C57BL/6 mice were randomized into three groups fed: (1) 0.1 mg/kg Se (non-IR control group), (2) 0.8 mg/kg Se (IR control group), and (3) 0.8 mg/kg Se with Bet supplementation (IR+Bet intervention group). The experiment was conducted in two phases: a 4-month period of IR induction via high-Se diet, followed by a 1-month Bet intervention period. Plasma Se, insulin, and fasting glucose levels were assessed at baseline, and both before and after Bet intervention. Plasma homocysteine, lipid profiles (HDL, LDL, TCHO, TG), as well as glucose tolerance tests and insulin tolerance tests, were measured before and after intervention. After euthanasia, Se content, selenoprotein levels, and the expression of enzymes related to Ser synthesis and metabolism were measured in various tissues. After 1 month of Bet supplementation, mice in the IR+Bet intervention group exhibited significantly higher insulin sensitivity in ITT (P<.01), and lower expression of PHGDH in liver, skeletal muscle, and pancreas tissues (P<.05), compared to the IR control group. Additionally, plasma lipid profiles were significantly improved in the IR+Bet intervention group (P<.05). This is the first report demonstrating that Bet supplementation, like exogenous Ser, can effectively improve hyperglycemia and insulin resistance in mice fed a high-Se diet.

目的：我们之前的研究表明，外源性丝氨酸可能作为SAM生物合成的甲基供体，改善了饲料中含有0.8mg/kg硒的C57BL/6小鼠的胰岛素抵抗。本研究旨在研究甜菜碱，一种替代的甲基供体，是否可以类似地减轻小鼠高硒诱导的IR。方法：将30只C57BL/6小鼠随机分为3组：(1)0.1mg/kg硒（非IR对照组）、(2)0.8mg/kg硒（IR对照组）和(3)0.8mg/kg硒加Bet （IR + Bet干预组）。试验分两个阶段进行：高硒饮食诱导IR 4个月，Bet干预1个月。血浆硒、胰岛素和空腹血糖水平在基线时以及Bet干预前后进行评估。测量干预前后血浆同型半胱氨酸、血脂（HDL、LDL、TCHO、TG）、葡萄糖耐量试验和胰岛素耐量试验。安乐死后，测定各组组织中硒含量、硒蛋白水平以及与硒合成和代谢相关的酶的表达。结果：在补充Bet一个月后，与IR对照组相比，IR + Bet干预组小鼠的ITT胰岛素敏感性显著提高（P < 0.01），肝脏、骨骼肌和胰腺组织中PHGDH表达显著降低（P < 0.05）。此外，IR + Bet干预组血浆脂质谱显著改善（P < 0.05）。结论：这是首次有报道表明补充Bet可以像外源性Ser一样，有效改善高硒小鼠的高血糖和胰岛素抵抗。

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引用次数: 0

Olive-derived elenolic acid surpasses metformin and rivals liraglutide in managing blood glucose and obesity in a mouse model of type 2 diabetes 在2型糖尿病小鼠模型中，橄榄衍生的烯醇酸在控制血糖和肥胖方面超过二甲双胍，并与利拉鲁肽竞争。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-26 DOI: 10.1016/j.jnutbio.2025.110206

Yao Wang , Hana Alkhalidy , Xinyi Cao , Reagan Vaughan , MD Abu T. Rachi , Bin Xu , Balaji Kale , Abeje Silte , Jennifer Rainville , Georgia E. Hodes , Yan Zhang , Dongmin Liu

Obesity and type 2 diabetes (T2D) are among the most common metabolic diseases that are associated with increased risk of noncommunicable diseases globally. Elenolic acid (EA), derived from olives, was shown to possess potent acute effects on obesity and diabetes that were associated with increased gut hormone secretion. Here, we investigate the long-term effects of EA in two mouse models of obesity and diabetes. In diet-induced obese mice, oral administration of EA (50 mg/kg/day) for 7 weeks, normalized fasting blood glucose (from 176.6±4.5 mg/dL to 120.8±4.0 mg/dL), and restored glucose tolerance and insulin sensitivity to levels comparable to lean mice. These improvements were associated with increased circulating peptide YY and gastric inhibitory polypeptide concentrations, downregulation of hypothalamic agouti-related peptide (AgRP), reduced food intake (∼20%), and weight loss. Acutely, EA slowed gastric emptying rate by about 50% and increased glucagon like peptide-1 levels. In db/db mice, EA reduced non-fasting blood glucose from 459.0±51.1 mg/dL to 208.9±10.3 mg/dL, an effect comparable to liraglutide and greater than metformin. EA also lowered fasting blood glucose levels similar to liraglutide and significantly below those observed with metformin. Moreover, EA-treated mice exhibited less weight gain than those receiving either drug. These effects were accompanied by decreased AgRP expression and increased c-fos activation. These results suggest that EA is a novel, multi-target agent with therapeutic potential for treating T2D and obesity.

肥胖和2型糖尿病是与全球非传染性疾病风险增加相关的最常见代谢性疾病。从橄榄中提取的烯醇酸（EA）被证明对肥胖和糖尿病具有强大的急性作用，这与肠道激素分泌增加有关。在这里，我们研究了EA对肥胖和糖尿病两种小鼠模型的长期影响。在饮食诱导的肥胖小鼠中，口服EA （50 mg/kg/天）7周，空腹血糖正常（从176.6±4.5 mg/dl降至120.8±4.0 mg/dl），葡萄糖耐量和胰岛素敏感性恢复到与瘦小鼠相当的水平。这些改善与循环肽YY和胃抑制性多肽浓度增加、下丘脑AgRP相关肽（AgRP）下调、食物摄入量减少（~ 20%）和体重减轻有关。急性时，EA使胃排空速度减慢约50%，并使胰高血糖素样肽-1水平升高。在db/db小鼠中，EA将非空腹血糖从459.0±51.1 mg/dl降至208.9±10.3 mg/dl，效果与利拉鲁肽相当，优于二甲双胍。EA还降低了空腹血糖水平，与利拉鲁肽相似，显著低于二甲双胍。此外，ea治疗的小鼠比服用任何一种药物的小鼠表现出更少的体重增加。这些影响伴随着下丘脑AgRP表达减少和c-fos激活增加。这些结果表明，EA是一种新型的多靶点药物，具有治疗T2D和肥胖的潜力。

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引用次数: 0

Dietary dipeptide γ-glutamyl valine (γ-EV) activates AMPK and improves glucose homeostasis in db/db mice 膳食二肽g-谷氨酰缬氨酸（g-EV）激活AMPK并改善db/db小鼠葡萄糖稳态。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-26 DOI: 10.1016/j.jnutbio.2025.110204

Bikram Upadhyaya , Chia-Sin Liew , Jean-Jack M Riethoven , Yoshinori Mine , Kaustav Majumder

This study investigates the therapeutic potential of γ-glutamyl valine (γ-EV) in 4 week-old male db/db mice, a well-established model for type 2 diabetes. Mice were fed an AIN-93 G diet and administered γ-EV (500 mg/kg body weight) via drinking water for 3 weeks. Blood, liver, muscle, and intestinal tissues were collected to assess blood glucose, peptide bioavailability, liver function, glycogen levels, protein expression, and transcriptomic changes. γ-EV was bioavailable in circulation (2.07±1.59 μM) and significantly improved food efficiency (+79%, P<.0001), despite reduced calorie intake (-27%, P<.0001). Treated mice exhibited markedly reduced polyuria and water intake (−80%, P<.0001), and showed substantial reductions in blood glucose under both fasted (−76%, P<.0001) and non-fasted (−29%, P=.0054) conditions. Although γ-EV increased the hepatosomatic index (+66%, P<.0001), serum ALT levels remained unchanged (P=.0765), indicating no hepatotoxicity. RNA-seq revealed 1308 differentially expressed genes in the liver and 147 in the jejunum, with 26 genes overlapping between the two. Key upregulated GO terms included fatty acid metabolism (jejunum) and oxidoreductase activity (liver). Hepatic p-AMPKα levels increased (+86%, P=.0137) alongside decreased liver glycogen (−79%, P<.0001), suggesting γ-EV induces beneficial catabolic signaling. Overall, γ-EV shows promise as an anti-diabetic peptide.

本研究探讨了g-谷氨酰缬氨酸（g-EV）在4周龄雄性db/db小鼠（一种成熟的2型糖尿病模型）中的治疗潜力。小鼠饲喂AIN-93G日粮，并通过饮水给予g-EV （500 mg/kg体重），连续3周。采集血液、肝脏、肌肉和肠道组织，评估血糖、肽生物利用度、肝功能、糖原水平、蛋白质表达和转录组变化。g-EV在循环中具有生物利用度（2.07±1.59 μM），在减少热量摄入（-27%,P < 0.0001）的情况下，显著提高了食物效率（+79%,P < 0.0001）。治疗后的小鼠多尿和饮水量明显减少（-80%,P < 0.0001），空腹（-76%,P < 0.0001）和非空腹（-29%,P = 0.0054）情况下的血糖均显著降低。虽然g-EV增加了肝体指数（+66%,P < 0.0001），但血清ALT水平保持不变（P = 0.0765），表明无肝毒性。RNA-Seq显示，1308个差异表达基因在肝脏，147个差异表达基因在空肠，其中26个基因在两者之间重叠。氧化石墨烯上调的关键因素包括脂肪酸代谢（空肠）和氧化还原酶活性（肝脏）。肝脏P - ampk α水平升高（+86%,P = 0.0137），同时肝糖原降低（-79%,P < 0.0001），提示g-EV诱导有益的分解代谢信号。总的来说，g-EV作为一种抗糖尿病肽显示出了前景。

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引用次数: 0