Journal of Nutritional Biochemistry最新文献_第5页

Dietary methylglyoxal induces renal lipotoxicity primarily through adipose tissue dysfunction in mice fed normal or obesogenic high-fat diets 在喂食正常或致肥性高脂饮食的小鼠中，膳食甲基乙二醛主要通过脂肪组织功能障碍诱导肾脏脂肪毒性。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-24 DOI: 10.1016/j.jnutbio.2025.110244

Medhavi Paramita Kondanna , Yu-Ho Chang , Hsin-Yi Yang , Chi-Hao Wu , Wan-Ju Yeh

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.

不健康的饮食模式可能通过饮食中甲基乙二醛（MG）和晚期糖基化终产物（AGEs）的升高而损害肾功能。虽然脂肪组织储存甘油三酯（TG），但其功能障碍促进异位脂毒性，MG或AGEs加剧了这一过程。本研究调查了长期膳食MG是否会引起由脂肪组织功能障碍和异位脂质沉积介导的肾脏损害。将8周龄雄性ICR小鼠随机分为正常饮食和致肥性高脂饮食（HFD）四组，每组在饮用水中添加或不添加1% MG，持续52周。HFD显著增加了脂肪组织和肾脏的MG-AGEs。虽然它引起脂肪细胞肥大，但在缺乏肾脂质积累的情况下，仍观察到hfd诱导的肾损伤。同时，MG引起肾脂毒性和损伤，表现为皮质和髓质的TG浓度升高。在饲喂hfd的小鼠中，MG通过抑制血管生成和增加间质胶原积累进一步加重了脂肪组织功能障碍。此外，MG联合给药减少了脂肪细胞的大小，这一发现与HFD单独引起的肥大相反。此外，在这些喂食hfd的小鼠肾脏中，MG导致髓质TG浓度升高和胶原表达升高。总之，HFD单独引起非脂毒性肾损伤，没有明显的脂肪功能障碍。然而，无论饮食如何，MG给药都会引起脂肪组织功能障碍和进行性肾脂毒性。这些研究结果表明，MG诱导的肾脏损伤主要是由脂肪组织功能障碍介导的，这就建立了膳食MG摄入量与肾脏疾病进展之间的关键联系，而不依赖于致肥性饮食状态。

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引用次数: 0

Lnc-Gm26626 in visceral adipose tissues participates in energy metabolism via IDH3α-associated tricarboxylic acid cycle activity 内脏脂肪组织中的Lnc-Gm26626通过idh3 α-相关三羧酸循环活性参与能量代谢。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-21 DOI: 10.1016/j.jnutbio.2025.110243

Haoneng Tang , Fen Xiao , Yaru Chen , Chenyi Tang , Yue Guo , Huixuan Wu , Yinghui Zhou , Houde Zhou

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.

背景：在禁食和再喂养条件下，发现参与内脏脂肪组织发育的新型长链非编码rna （lncRNAs）可能有助于揭示饮食诱导肥胖的机制。方法：对成年小鼠进行禁食和再喂养干预，提取肠系膜脂肪组织进行转录组测序。鉴定了Lnc-Gm26626，并利用腺病毒介导的基因干扰研究了其在三羧酸循环（TCA）和异柠檬酸脱氢酶3α (IDH3α)表达中的作用。进一步进行体内实验，明确lnc-Gm26626是否影响脂肪组织的可塑性。结果：共鉴定出3570个差异表达lncrna和5032个差异表达mrna， lnc-Gm26626受外部营养刺激调控，并在高糖条件下观察到从细胞核向细胞质转运。lnc-Gm26626的敲低可抑制体外IDH3α的表达；aav介导的lnc-Gm26626基因敲低增加了肠系膜脂肪组织的脂肪含量，缓解了禁食和再喂养时糖脂代谢的波动。结论：我们发现lnc-Gm26626是一种新的能量代谢调节剂，通过调节TCA循环中IDH3α的表达参与能量限制的反应，从而影响雄性小鼠内脏脂肪组织的可塑性。

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引用次数: 0

Electroconvulsive therapy modulates brain plasticity in male depression: Links to gut microbial metabolites and diet-derived regulation of Wnt/BDNF signaling 电休克疗法调节男性抑郁症的大脑可塑性：与肠道微生物代谢物和饮食来源的Wnt/BDNF信号调节有关

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-20 DOI: 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.

电休克疗法（ECT）是治疗难治性抑郁症最有效的干预手段；然而，其与饮食调节肠脑轴的相互作用尚未得到充分探讨。本研究旨在阐明电痉挛、肠道菌群重塑、短链脂肪酸（SCFA）产生和神经可塑性之间的机制联系。本研究将小鼠置于慢性约束应激（6 h/d，连续28天）下，建立抑郁样模型。利用结合行为评估、多模态神经成像技术（如PET-CT和激光散斑对比成像）以及多组学分析（包括宏基因组学、代谢组学和转录组学）的转化方法，我们在啮齿动物模型中证明了ECT诱导了显著的肠道微生物群重塑，其特征是乳酸杆菌和双歧杆菌等产生scfa的菌群富集。这种重塑与肠屏障完整性恢复和血浆SCFA水平升高有关。在机制上，这些微生物代谢物激活了海马Wnt/β-catenin信号通路，增强了突触可塑性的恢复，而同时补充益生菌通过scfa依赖的表观遗传机制进一步放大了脑源性神经营养因子（BDNF）的表达。神经影像学证实ect后脑糖代谢和血流动力学功能恢复正常。总之，我们的发现揭示了一种新的肠-脑通讯途径，ECT通过该途径发挥其抗抑郁作用，将scfa定位为连接微生物代谢改变和神经可塑性的重要介质。这项研究不仅重新定义了营养生物化学在神经调节中的作用，而且还提示了微生物代谢物监测在定制抗抑郁治疗以提高疗效方面的潜力。

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引用次数: 0

Prebiotic fructan chain length influences enteric microbiota-host GABAergic signaling and intestinal motility 益生元果聚糖链长度影响肠道微生物-宿主gaba能信号传导和肠道运动。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-19 DOI: 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.

膳食纤维的摄入对肠道运动和肠道微生物群的结构和功能具有重要的调节作用。然而，纤维之间细微的结构差异在多大程度上通过微生物-宿主相互作用调节运动仍未确定。GABA是一种微生物代谢物，与微生物果聚糖发酵和宿主肠道运动密切相关。本研究的目的是研究果聚糖链长度如何影响肠道和结肠收缩背后的微生物-宿主信号。雄性和雌性小鼠配对喂食不含纤维的饮食（无纤维饮食，FFD）或含有纤维素（CELL，纤维对照）、短链低聚果糖（scFOS）或菊粉（INU）的饮食，为期两周。与FFD相比，scFOS和INU同样提高了回肠和结肠中总微生物负荷（荧光原位杂交）、GABA合成细菌的相对丰度（16S rRNA测序）和腔内GABA浓度（ELISA）。相反，与INU相比，scFOS改变了回肠中更多的运动和gaba相关基因的表达（Fluidigm qPCR），而INU在结肠中比scFOS改变了更多的运动和gaba相关基因的表达。用GABA孵育回肠段可增强INU体内的收缩力，但对scFOS没有作用。相反，加GABA的结肠段孵育抑制了scFOS的收缩力，使其降低到加或不加GABA的INU中观察到的水平。值得注意的是，GABA只改变了雌性小鼠的收缩力。我们的研究强调了饮食中的果聚糖链长度是gaba介导的节段性和性别特异性肠道运动的决定因素，并为研究益生元纤维结构如何影响微生物-宿主相互作用和生理创造了理论基础和框架。

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引用次数: 0

Diosmetin alleviates hyperuricemic nephropathy by activating the BNIP3/Nrf2/GPX4 pathway to inhibit ferroptosis of renal tubular epithelial cells induced by monosodium urate crystals diometin通过激活BNIP3/Nrf2/GPX4通路抑制尿酸钠晶体诱导的肾小管上皮细胞铁下垂，减轻高尿酸血症肾病。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-19 DOI: 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.

高尿酸血症肾病（HN）是高尿酸血症的严重肾脏并发症，但缺乏有效的治疗方法。铁死亡是一种由脂质过氧化驱动的铁依赖性细胞死亡形式，与肾小管损伤有关，但其在HN中的调节机制尚不清楚。本研究探讨了具有抗氧化作用的天然类黄酮薯蓣皂苷（diostin， DIOS）对尿酸钠（MSU）诱导的人肾小管细胞HK-2损伤的保护作用。我们证实msu诱导的细胞死亡是铁下垂的特征。通过转录组学分析和网络药理学的结合，我们确定了BNIP3/Nrf2/GPX4通路是DIOS的主要潜在靶点。分子对接和随后的实验验证表明，DIOS直接与BNIP3相互作用并调节BNIP3，导致Nrf2的激活及其下游靶标GPX4的上调。这个级联增强了细胞的抗氧化防御系统，有效地抑制了脂质过氧化和铁下垂。我们的研究结果揭示了DIOS保护msu诱导的肾小管损伤的新机制，并强调BNIP3/Nrf2/GPX4轴是减轻HN铁下垂的有希望的治疗靶点。

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引用次数: 0

Naringenin prevents osteoblast senescence in d-galactose-induced aging conditions via estrogen receptor-mediated pathway 柚皮素通过雌激素受体介导的途径防止d -半乳糖诱导的衰老条件下的成骨细胞衰老。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-17 DOI: 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.

柚皮素是一种植物来源的类黄酮，具有抗增殖、抗炎和抗血管生成的特性，可以对抗各种代谢紊乱。虽然有报道表明柚皮素具有成骨潜能，但其在老年性骨质疏松症中的作用仍未得到充分研究。本研究旨在探讨柚皮素对d -半乳糖（D-gal）诱导的老年性骨质疏松的保护作用。D-gal老化骨质流失动物模型的结果表明，柚皮素改善骨微结构，促进离体矿化，改变骨血清标志物。为了验证柚皮素保护作用背后的作用方式，我们在细胞水平上进行了进一步的实验。柚皮素促进成骨细胞分化，抑制D-gal刺激后成骨细胞的衰老、凋亡和细胞活性氧（ROS）的产生。在机制上，柚皮素通过雌激素受体介导的途径减缓衰老，当雌激素途径抑制剂ICI182.780处理颅骨成骨细胞时，其有效性大大降低。综上所述，这些结果使我们得出结论，柚皮素可能作为一种潜在的治疗老年骨质疏松症的药物。

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引用次数: 0

Sulforaphane ameliorates DSS-induced colitis and secondary liver injury in mice: Proposed mechanism in the SCFAs-FFAR2/3-macrophage polarization axis 萝卜硫素改善dss诱导的小鼠结肠炎和继发性肝损伤：scfas - ffar2 /3-巨噬细胞极化轴的可能机制

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-16 DOI: 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.

萝卜硫素（SFN）是一种从十字花科蔬菜中提取的异硫氰酸盐，已显示出治疗炎症性疾病的潜力。我们之前的研究表明，SFN可以改善葡聚糖硫酸钠（DSS）诱导小鼠的溃疡性结肠炎（UC）并恢复肠道微生物群组成。在本研究中，我们进一步研究了SFN对UC继发性肝损伤的保护作用和潜在机制。结果显示，SFN可显著减轻dss诱导结肠炎小鼠结肠和肝脏病理损伤，改善肝功能参数，上调肠道紧密连接蛋白和Muc2表达，抑制炎症反应。此外，SFN显著提高短链脂肪酸（SCFA）浓度，增强SCFA受体（游离脂肪酸受体2和3，FFAR2/3）的表达，并通过抑制结肠和肝脏中M1和促进M2表型来调节巨噬细胞极化。总之，这些发现表明SFN可能通过增强肠屏障功能和减少炎症反应来减轻结肠炎和继发性肝损伤，可能通过scfas - ffar2 /3-巨噬细胞极化信号级联。因此，SFN可能作为一种很有前途的辅助治疗剂用于UC的预防和治疗。

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引用次数: 0

Effects of pubertal dietary energy-protein levels and breeding strategies on mammary gland development and lactational performance in mice 青春期饲粮能量蛋白水平和饲养策略对小鼠乳腺发育和泌乳性能的影响。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-15 DOI: 10.1016/j.jnutbio.2025.110236

Xusheng Dong , Siyu Tian , Wenjing Yu, Xueyan Lin, Zhonghua Wang, Qiuling Hou

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.

确定膳食能量和蛋白质水平以加速小母牛生长，同时确保乳房发育仍然具有挑战性。牛的技术和经济限制阻碍了确定最佳能量蛋白质水平和繁殖时间。因此，我们使用小鼠作为模型来研究断奶后不同能量和蛋白质浓度的饮食，结合两种繁殖策略，如何影响乳房发育和泌乳。将240只雌性小鼠（21 d）分为5组：高能中蛋白组（HM）、高能低蛋白组（HL）、中能量中蛋白组（MM）、低能量中蛋白组（LM）和低能量低蛋白组（LL）。在目标交配体重（27±1 g）和体成熟（56 d）时采集乳腺组织和血清。在达到目标体重时或在63日龄时开始饲养，在妊娠15d时采集乳腺和血清样本，在哺乳13d时采集血清样本。结果表明，适度增加饲粮能量可促进小鼠生长，促进乳腺发育，提高泌乳性能。在低能量摄入的情况下，维持足够的蛋白质对乳房和整体生长至关重要。高能量喂养与基于体重的交配策略相结合显著提高了产奶量，而基于年龄的交配为营养受限的小鼠提供了必要的发育窗口。这些研究结果为在母牛管理中采用高能喂养策略来提高初产犊龄提供了理论基础。

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引用次数: 0

3,3′-Diindolylmethane ameliorate obesity-related skeletal muscle atrophy via regulating mitochondrial function 3,3'-二吲哚甲烷通过调节线粒体功能改善肥胖相关的骨骼肌萎缩。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-15 DOI: 10.1016/j.jnutbio.2025.110223

Yuquan Zhong , Siyuan Chen , Jingyun Pan , Ruomei Niu , Junqiang Du , Qiuxia Dong , Yanxi Liu , Yilu Yao , Yunfeng Lin , Heng Fang , Jiewen Su , Xudong Li , Yan Zhang , Guangyu Yang , Jinyin Wu , Juntao Li , Weiwen Liu , Bing Huang , Jie Tang , Wei Zhu

Skeletal muscle is the primary storage and metabolic site for amino acids and proteins in the body, and its mass and function are affected by various pathological factors. Studies have shown that mitochondrial dysfunction is associated with skeletal muscle atrophy. Indole-3-carbinol (I3C) and its active metabolite 3,3′-Diindolylmethane (DIM) have bioactivities such as inhibiting fat formation, but it is unclear whether they can affect skeletal muscle atrophy in obesity by improving mitochondrial function. Our research found that high-fat factors can induce obesity-related skeletal muscle atrophy, characterized by decreased muscle mass and function, reduced mitochondrial number, and impaired function in muscle cells. DIM can improve obesity-related skeletal muscle atrophy caused by a high-fat diet, and the mechanism may be related to the regulation of AMPK/SIRT1/PGC-1α pathway protein expression and improved mitochondrial function in muscle cells.

骨骼肌是人体氨基酸和蛋白质的主要储存和代谢部位，其质量和功能受到多种病理因素的影响。研究表明，线粒体功能障碍与骨骼肌萎缩有关。吲哚-3-甲醇（I3C）及其活性代谢物3,3′-二吲哚基甲烷（DIM）具有抑制脂肪形成等生物活性，但是否通过改善线粒体功能影响肥胖骨骼肌萎缩尚不清楚。我们的研究发现，高脂因子可诱导肥胖相关的骨骼肌萎缩，表现为肌肉质量和功能下降，线粒体数量减少，肌肉细胞功能受损。DIM可改善高脂饮食引起的肥胖相关性骨骼肌萎缩，其机制可能与调节AMPK/SIRT1/PGC-1α通路蛋白表达及改善肌肉细胞线粒体功能有关。

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引用次数: 0

Ketogenic diet attenuates high fat diet induced obesity in rats: insights into hepatic and intestinal tissues 生酮饮食减轻大鼠高脂肪饮食引起的肥胖：对肝脏和肠道组织的见解。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-12-13 DOI: 10.1016/j.jnutbio.2025.110237

Nada F. Abo El-Magd , Nehal M. Ramadan , Yomna F. Hassan , Amr M. Mahmoud , Maha M. Azzam , Salma M. Eraky

The rising global prevalence of obesity and its impact on health and economy make finding available safe treatment an urgent need. Ketogenic diet represents trendy dietary intervention, while underlying molecular mechanisms remains unclear. Twenty-four male Sprague-Dawley rats were randomized into three groups: Control (maintained on conventional chow diet for 24 weeks), HFD (fed High-fat diet (HFD) for 24 weeks), keto (fed HFD for 12 weeks, then ketogenic diet for additional 12 weeks). Effect of ketogenic diet on serum metabolomics using Ultra Performance Liquid Chromatography coupled with Liquid Chromatography on both positive and negative modes; hepatic tissue using histopathological examination, enzyme-linked immunosorbent assay (ELISA), Real time Polymerase Chain Reaction, proteome array detection; intestinal tissue using histopathological examination, ELISA and adipose tissue using histopathological examination were evaluated. The ketogenic diet reduced rat weight, food intake, epididymal fat mass, and blood glucose level compared to HFD group. Furthermore, it resulted in a decrease in serum methionine, linolenic acid, Lyso Phosphatidylcholine (PC) (15.0:0.0), Lyso PC (18.0:0.0) with hepatic repression of fibroblast growth factor 21 (FGF21), and type II cell surface protein/ Dipeptidyl peptidase 4, Intercellular Adhesion Molecule 1, Insulin growth factor-1, Lipocalin-2, Serpin E1, tissue inhibitor of matrix metalloproteinase-1, receptor for advanced glycation end products and induction of Farnesoid X receptor (FXR), hepatocyte growth factor (HGF) which leads to hepatic antioxidant effects and histopathological amelioration. In addition, the ketogenic diet caused intestinal induction of melanocortin-4 receptors/ glucagon-like peptide 1 pathway, which causes intestinal antioxidant effects and histopathological amelioration. Thus, ketogenic diet stated potential anti-obesity effect that mitigates HFD-induced organ damage through the modulation of key metabolic and signaling networks.

全球肥胖流行率不断上升及其对健康和经济的影响，迫切需要找到可用的安全治疗方法。生酮饮食代表了流行的饮食干预，但其潜在的分子机制尚不清楚。将24只雄性Sprague-Dawley大鼠随机分为3组：对照组（喂食常规饲料24周）、高脂饲料（喂食高脂饲料24周）、酮饲料（喂食高脂饲料12周，再喂食生酮饲料12周）。生酮饮食对血清代谢组学的影响——超高效液相色谱-正、负两种模式肝组织采用组织病理学检查、酶联免疫吸附试验（ELISA）、实时聚合酶链反应、蛋白质组阵列检测；采用组织病理学检查对大鼠肠道组织、ELISA和脂肪组织进行评价。与HFD组相比，生酮饮食降低了大鼠体重、食物摄入量、附睾脂肪量和血糖水平。此外，它还导致血清蛋氨酸、亚麻酸、Lyso磷脂酰胆碱（PC）（15.0:0.0）、Lyso磷脂酰胆碱（PC）（18.0:0.0）的降低，并抑制成纤维细胞生长因子21 （FGF21）、II型细胞表面蛋白/二肽基肽酶4、细胞间粘附分子1、胰岛素生长因子-1、脂钙素-2、丝氨酸蛋白酶E1、基质金属蛋白酶-1组织抑制剂、晚期糖基化终产物受体和Farnesoid X受体（FXR）的诱导。肝细胞生长因子（HGF），导致肝脏抗氧化作用和组织病理学改善。此外，生酮饮食引起肠道诱导黑素皮质素-4受体/胰高血糖素样肽1通路，引起肠道抗氧化作用和组织病理改善。因此，生酮饮食表明了潜在的抗肥胖作用，通过调节关键的代谢和信号网络来减轻hfd诱导的器官损伤。

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