Journal of Nutritional Biochemistry最新文献_第4页

Hypothyroidism induced by excessive-iodine is associated in humans with altered hsa-miR-199a-5p/HIF-1α axis and thyroglobulin 过量碘引起的甲状腺功能减退与hsa-miR-199a-5p/HIF-1α轴和甲状腺球蛋白的改变有关。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-01-11 DOI: 10.1016/j.jnutbio.2025.109841

Jing He , Yishan Dong , Xianglan Chen , Shuo Wang , Zheng Shen , Xu Huang , Weijia Li , Zhihan Yang , Jin Cheng , Jinyu Li , Qiaoling Liu , Ziqi Xu , Dianjun Sun , Wei Zhang

The adverse effect of excessive iodine intake has attracted extensive attention. However, the role of excessive iodine on hypothyroidism and detailed mechanism are not exactly known. Studies have shown that miRNAs are crucial to the occurrence and development of hypothyroidism. Nevertheless, there still limited population-based studies on the miRNA-mRNA regulation in the occurrence of hypothyroidism induced by excessive iodine. Total of 291 hypothyroidism patients and 291 controls matched by sex (1:1) and age (±3 years) were enrolled from Heze City, Shandong Province. Multiple logistic regression analysis revealed that water iodine concentration of 100–300 µg/L was an independent risk factor for hypothyroidism. Additionally, excessive water iodine was associated with an increase in thyroglobulin (Tg) concentration in new diagnosed hypothyroidism patients. Further, high-throughput miRNA sequencing indicated that hsa-miR-19b-3p, hsa-miR-199a-5p, hsa-miR-204-5p and hsa-miR-144-3p were significantly correlated with the occurrence of hypothyroidism. Q-PCR results showed that levels of hsa-miR-199a-5p and hsa-miR-204-5p in the hypothyroidism group were markedly lower than those in the control group. In addition, among the hypothyroidism patients, hsa-miR-199a-5p level in water iodine >100 µg/L group was remarkably higher than that in 10-100 µg/L group. Furthermore, HIF-1α and PD-L1 mRNA levels in whole blood were determined, which are the target genes regulated by miRNA-199a-5p in previous studies. Compared with the control group, HIF-1α mRNA level was significantly increased in the hypothyroidism group. In the hypothyroidism case group, compared with the 10–100 µg/L group, HIF-1α mRNA level was remarkably decreased in water iodine >100 µg/L group. Collectively, miR-199a-5p/HIF-1α axis may contribute to hypothyroidism induced by excessive iodine through thyroglobulin.

碘摄入过量的不良影响已引起广泛关注。然而，过量碘对甲状腺功能减退的作用和具体机制尚不清楚。研究表明，mirna在甲状腺功能减退症的发生和发展中起着至关重要的作用。然而，关于miRNA-mRNA在过量碘致甲状腺功能减退发生中的调控作用的基于人群的研究仍然有限。选取山东省菏泽市甲状腺功能减退症患者291例，按性别（1:1）和年龄（±3岁）匹配的对照组291例。多元logistic回归分析显示，水中碘浓度100 ~ 300μg/L是甲状腺功能减退的独立危险因素。此外，在新诊断的甲状腺功能减退患者中，过量的水碘与甲状腺球蛋白（Tg）浓度升高有关。此外，高通量miRNA测序显示，hsa-miR-19b-3p、hsa-miR-199a-5p、hsa-miR-204-5p和hsa-miR-144-3p与甲状腺功能减退的发生显著相关。Q-PCR结果显示，甲状腺功能减退组hsa-miR-199a-5p、hsa-miR-204-5p水平明显低于对照组。此外，在甲状腺功能减退患者中，水碘bbb100 μg/L组hsa-miR-199a-5p水平显著高于10-100μg/L组。进一步测定全血HIF-1α和PD-L1 mRNA水平，这是以往研究中miRNA-199a-5p调控的靶基因。与对照组相比，甲状腺功能减退组HIF-1α mRNA水平显著升高。在甲状腺功能减退病例组中，与10-100µg/L水碘组相比，水碘>100µg/L组HIF-1α mRNA水平显著降低。总之，miR-199a-5p/HIF-1α轴可能通过甲状腺球蛋白参与过量碘诱导的甲状腺功能减退。

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引用次数: 0

The supply of branched-chain amino acids and branched-chain keto acids alter lipid metabolism, oxidative stress, and apoptosis in primary bovine hepatocytes 支链氨基酸和支链酮酸的供应改变了原代牛肝细胞的脂质代谢、氧化应激和凋亡。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-01-11 DOI: 10.1016/j.jnutbio.2025.109839

Jayasimha R. Daddam , Mounica Sura , Daniel Vocelle , Juliana G. Laguna , Kristen Gallagher , Zheng Zhou

Fatty liver impairs liver function and reduces productivity in dairy cows. Our previous in vivo findings demonstrated that branched-chain amino acids (BCAA) or branched-chain ketoacid (BCKA) improved liver function and lactation performance in dairy cows; however, the underlying mechanisms remain unclear. This study aimed to assess the impact of BCAA or BCKA supplementation on intracellular triglyceride (TG) accumulation, lipid metabolism, antioxidant response, and apoptosis in hepatocytes. Treatments were: control (CON): customized medium with amino acids, volatile fatty acids, fatty acids (FA), glucose, choline, insulin, and albumin concentrations equal to circulating levels in cows 4d postpartum; BCAA: CON + 33% additional BCAA of plasma BCAA 4d postpartum; and BCKA: CON + 33% additional BCKA of plasma BCAA 4d postpartum. Compared to CON, BCAA and BCKA reduced intracellular TG concentration by 32% and 40%, respectively, after 72h. BCAA and BCKA enhanced the uptake of palmitic acid, but upregulated the expression of genes regulating FA oxidation. Although mitochondrial membrane potential was reduced, oxidative protein damage (protein carbonyl levels) was decreased in BCAA- and BCKA-treated hepatocytes without changes in mitochondrial copy number. Additionally, compared to CON, BCAA and BCKA decreased the expression of executioner caspases (caspase 3 and caspase 7) and reduced the portion of hepatocytes with activated caspase 3/7, suggesting reduced apoptosis. These findings suggest that BCAA or BCKA supplementation improves hepatocyte lipid metabolism, antioxidant defenses, and apoptosis regulation, potentially mitigating the adverse effects of fatty liver. These mechanisms likely underlie the previously observed improvements in liver function and lactation performance.

脂肪肝损害奶牛的肝功能，降低奶牛的生产能力。我们之前的体内研究结果表明，支链氨基酸（BCAA）或支链酮酸（BCKA）可以改善奶牛的肝功能和泌乳性能；然而，潜在的机制仍不清楚。本研究旨在评估补充BCAA或BCKA对肝细胞内甘油三酯（TG）积累、脂质代谢、抗氧化反应和细胞凋亡的影响。对照组（CON）：定制培养基，其氨基酸、挥发性脂肪酸、脂肪酸（FA）、葡萄糖、胆碱、胰岛素和白蛋白浓度等于产后4d奶牛循环水平；BCAA: CON + 产后4d血浆BCAA增加33%；BCKA: CON + 产后4d血浆BCAA增加33% BCKA。与CON相比，72h后，BCAA和BCKA分别使细胞内TG浓度降低32%和40%。BCAA和BCKA增强了棕榈酸的摄取，但上调了FA氧化调控基因的表达。BCAA-和bcka处理的肝细胞虽然线粒体膜电位降低，但氧化蛋白损伤（蛋白羰基水平）降低，线粒体拷贝数没有变化。此外，与CON相比，BCAA和BCKA降低了刽子手caspase （caspase 3和caspase 7）的表达，减少了caspase 3/7活化的肝细胞比例，表明凋亡减少。这些发现表明，补充BCAA或BCKA可改善肝细胞脂质代谢、抗氧化防御和细胞凋亡调节，可能减轻脂肪肝的不良影响。这些机制可能是先前观察到的肝功能和泌乳性能改善的基础。

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引用次数: 0

Effect of reduced placental expression of zinc transporters on selective intrauterine growth restriction in monochorionic diamniotic twin pregnancies 胎盘锌转运蛋白表达降低对双羊膜双胎妊娠选择性宫内生长限制的影响。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-01-10 DOI: 10.1016/j.jnutbio.2025.109840

Tingting Xu , Yao Kong , Qing Hu , Hua Liao , Chunyan Deng , Xiaodong Wang , Haiyan Yu

Zinc is an essential trace element. The regulatory mechanism of zinc and its transporters in fetal growth in monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (MCDA-sIUGR) is unclear. A total of 45 MCDA twins were divided into two groups, MCDA (n=37) and MCDA-sIUGR (n=8), to investigate their possible effects on fetal growth. Maternal and fetal serum zinc levels were measured using a microassay. Immunohistochemistry and western blotting were performed to quantify the expression and localization of zinc transporters. Correlation scatter plots and matrices were used to test the correlation between maternal and cord serum zinc levels, placental zinc transporters, and fetal growth. There was a significant difference in fetal birth weight and placental weight among MCDA T_H (higher birth weight of twin), MCDA T_L (lower birth weight of twin), MCDA-sIUGR T_H, and MCDA-sIUGR T_L groups (P < .05), among which the MCDA-sIUGR T_L group was found to be significantly lower than the other three groups (P < .05). Placental zinc transporters, including Zip 2, metal regulatory transcription factor 1 (MTF 1), and ZnT1, were significantly decreased in the MCDA-sIUGR T_L group compared to those in the other three groups (P < .05). Furthermore, we observed varying degrees of correlation between fetal weight and maternal/fetal serum zinc levels and placental zinc transporters. Our study indicates that placental zinc transporters are impaired in MCDA-sIUGR, particularly in lightweight twins. Therefore, we hypothesized that the reduced placental expression of zinc transporters may affect fetal growth in MCDA twins.

锌是人体必需的微量元素。锌及其转运体在选择性宫内生长受限（MCDA- siugr）单绒毛膜双羊膜双胞胎（MCDA- siugr）胎儿生长中的调节机制尚不清楚。将45例MCDA双胞胎分为MCDA组（n=37）和MCDA- siugr组（n=8），探讨其对胎儿生长的可能影响。采用微量法测定孕妇和胎儿血清锌水平。免疫组织化学和免疫印迹法定量测定锌转运蛋白的表达和定位。使用相关散点图和矩阵来检验母体和脐带血清锌水平、胎盘锌转运蛋白和胎儿生长之间的相关性。MCDA TH组（双胎高出生体重）、MCDA TL组（双胎低出生体重）、MCDA- siugr TH组和MCDA- siugr TL组的胎儿出生体重和胎盘重量差异有统计学意义(pL组显著低于其他三组（pL组与其他三组比较差异有统计学意义）

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引用次数: 0

Resistant starch inhibits high-fat diet-induced oncogenic responses in the colon of C57BL/6 mice 抗性淀粉抑制C57BL/6小鼠结肠中高脂肪饮食诱导的致癌反应。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-01-07 DOI: 10.1016/j.jnutbio.2025.109838

Huawei Zeng , Bryan D. Safratowich , Zhenhua Liu , Michael R. Bukowski

The beneficial effects of dietary fiber for colon health may be due to short chain fatty acids (SCFAs), such as butyrate, produced by colonic bacterial fermentation. In contrast, obesogenic diet induced obesity is linked to increased colon cancer incidence. We hypothesize that increasing fiber intake promotes healthy microbiome and reduces bacterial dysbiosis and oncogenic signaling in the colon of mice fed an obesogenic diet. About 5-week-old male C57BL/6 mice were assigned to 5 dietary groups (n=22/group) for 24 weeks:(1) AIN93G as a control diet (AIN); (2) a high fat diet (HFD, 45% energy fat); (3) HFD+5% resistant starch enriched dietary fiber (RSF) from maize; (4) HFD+10%RSF; or (5) HFD+20%RSF. Compared to the AIN group, mice receiving the HFD exhibited more than 15% increase in body mass and body fat composition irrespective of RSF dosage. However, the HFD+RSF groups exhibited an increase (>300%) of fecal butyrate but a decrease (>45%) of secondary bile acids in a RSF dose-dependent manner over the HFD group. Similarly, there were concomitant decreases (>25%) in pro-inflammatory plasma cytokines (TNFα, IL-6 and MCP-1), β-catenin and Ki67 protein staining in the colon of the HFD+20%RSF group relative to the HFD group. Furthermore, the abundance of colonic Proteobacteria, signatures of dysbiosis, was decreased (>63%) in a RSF dose-dependent manner compared to the HFD. Collectively, these data indicate that RSF not only increases butyrate but also reduces secondary bile acids, bacterial dysbiosis and β-catenin in the colon of mice fed a HFD.

膳食纤维对结肠健康的有益作用可能是由于短链脂肪酸（SCFAs），如丁酸盐，由结肠细菌发酵产生。相反，致肥性饮食引起的肥胖与结肠癌发病率的增加有关。我们假设，增加纤维摄入量可以促进健康的微生物群，减少喂食致肥饮食的小鼠结肠中的细菌生态失调和致癌信号。5周龄雄性C57BL/6小鼠分为5个饲粮组（n= 22/组），连续24周：(1)以AIN93G为对照饲粮（AIN）；(2)高脂肪饮食（HFD， 45%能量脂肪）；(3) HFD+5%玉米抗性淀粉膳食纤维（RSF）；(4) rsf HFD + 10%;(5) HFD+20%RSF。与AIN组相比，无论RSF的剂量如何，接受HFD的小鼠的体重和体脂成分都增加了15%以上。然而，与HFD组相比，HFD+RSF组表现出粪便丁酸增加（> 300%），而次级胆汁酸减少（> 45%），并呈RSF剂量依赖性。同样，与HFD组相比，HFD+20%RSF组结肠中促炎血浆细胞因子（TNFα、IL-6和MCP-1）、β-catenin和Ki67蛋白染色也同时降低（bbb25 %）。此外，与HFD相比，结肠变形菌的丰度（失调的标志）以RSF剂量依赖的方式减少（bbbb63 %）。综上所述，这些数据表明，RSF不仅增加了喂食HFD小鼠的丁酸盐，还减少了次级胆汁酸、细菌生态失调和β-连环蛋白。

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引用次数: 0

Alternative splicing landscape in mouse skeletal muscle and adipose tissue: Effects of intermittent fasting and exercise 小鼠骨骼肌和脂肪组织的选择性剪接景观：间歇性禁食和运动的影响。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-12-25 DOI: 10.1016/j.jnutbio.2024.109837

Jasmin Gaugel , Markus Jähnert , Alexander Neumann , Florian Heyd , Annette Schürmann , Heike Vogel

Alternative splicing contributes to diversify the cellular protein landscape, but aberrant splicing is implicated in many diseases. To which extent mis-splicing contributes to insulin resistance as the causal defect of type 2 diabetes and whether this can be reversed by lifestyle interventions is largely unknown. Therefore, RNA sequencing data from skeletal muscle and adipose tissue of diabetes-susceptible NZO mice treated with or without intermittent fasting and of healthy C57BL/6J mice subjected to exercise were analyzed for alternative splicing differences using Whippet and rMATS. Diet and exercise interventions triggered comparable levels of splicing changes, although the splicing profile of skeletal muscle appeared to be more flexible than that of adipose tissue, with 72-114 differential splicing events in muscle and less than 25 in adipose tissue. Splicing changes induced by time-restricted feeding, alternate-day fasting and exercise were generally mild, with a maximal percent spliced in (PSI) difference of 67%, indicating that alternative splicing plays a rather minor role in lifestyle-induced adaptations of muscle and adipose tissue in mice. However, intron retention contributed to the regulation of gene expression, influencing genes whose expression was directly linked to phenotypic parameters (e.g. Eno2 and Pan2). Alternate-day fasting promoted skipping of exon 7 in Mlxipl (coding for ChREBP), thereby affecting the glucose sensing module of this carbohydrate-responsive transcription factor. Both intermittent fasting and exercise training led to alternative splicing of known diabetes-related GWAS genes (e.g. Abcc8, Ifnar2, Smarcad1), highlighting the potential metabolic relevance of these changes.

选择性剪接有助于使细胞蛋白质景观多样化，但异常剪接与许多疾病有关。错误剪接在多大程度上导致胰岛素抵抗作为2型糖尿病的因果缺陷，以及这是否可以通过生活方式干预来逆转在很大程度上是未知的。因此，使用Whippet和rMATS分析了间歇性禁食或不禁食治疗的糖尿病易感NZO小鼠和运动后健康C57BL/6J小鼠骨骼肌和脂肪组织的RNA测序数据，以确定剪接差异。饮食和运动干预引发了类似水平的剪接变化，尽管骨骼肌的剪接谱似乎比脂肪组织更灵活，肌肉中有72-114个不同的剪接事件，而脂肪组织中只有不到25个。限时摄食、隔日禁食和运动诱导的剪接变化通常是温和的，最大剪接百分比（PSI）差异为67%，表明选择性剪接在小鼠生活方式诱导的肌肉和脂肪组织适应中起着相当小的作用。然而，内含子保留有助于基因表达的调控，影响那些表达与表型参数直接相关的基因（如Eno2和Pan2）。隔日禁食促进了Mlxipl外显子7（编码ChREBP）的跳变，从而影响了这种碳水化合物应答转录因子的葡萄糖传感模块。间歇性禁食和运动训练都导致已知的糖尿病相关GWAS基因（如Abcc8、Ifnar2、Smarcad1）的选择性剪接，突出了这些变化的潜在代谢相关性。

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引用次数: 0

Protective potentials of extracted compound SILIBININ from milk thistle on type-2 diabetes mellitus and diesel exhaust particle (DEP) toxicity in experimental rats 水飞蓟提取物复方水飞蓟宾对2型糖尿病大鼠及柴油机尾气颗粒（DEP）毒性的保护作用。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-12-19 DOI: 10.1016/j.jnutbio.2024.109836

Olamide Olusegun Awolaja

The combustion of diesel in engines contributes polycyclic aromatic hydrocarbons to Diesel Particulate Matter (DPM) present in the atmosphere, therefore causing toxic mitigating consequences by eliciting oxidative modulation. Currently, type 2 diabetes mellitus is reported as a global menace, causing about 1.5 million deaths in 2019 and contributing to about 48% of related deaths among the populace aged below 70 years. (GBDCN, 2020). Silibinin (SIL) is a flavolignan from milk thistle with substantive therapeutic potential. This work elucidates the effects of SIL on glucose modulatory pathways (PI3K-AKT-GLUT 2 and AMPK-GLUT 2), inflammation and redox imbalance in the pancreas of diabetic rats subjected to DEP. Streptozocin was used to induce Type-2 diabetes mellitus in rats, which were further endangered to DEP (0.4 and 0.5 mg/kg) later, post-treated with SIL 40 mg/kg. For comparison, a parallel group of nondiabetic rats were exposed to DEP and afterwards treated with SIL, whilst the results were compared to the diabetic group. Results state that SIL leads to marked/substantial modulation in insulin-associated genes (PI3K, AKT, AMPK, GLUT 2), inflammatory markers (IL-1β, IL-10), peroxidation (MDA, CD) and antioxidative status (SOD, CAT, GPX, GSH, HO-1) in vivo as negatively induced by DEP and hyperglycaemia, thereby restoring glucose homeostasis. Taken together, SIL proffers the potential to ameliorate pancreatic-toxicity caused by DEP and high blood glucose/elevated glucose levels.

柴油在发动机中的燃烧为大气中的柴油颗粒物质（DPM）贡献了多环芳烃，因此通过引发氧化调节引起毒性减轻后果。目前，据报道，2型糖尿病是一种全球性威胁，2019年造成约150万人死亡，占70岁以下人口相关死亡人数的48%左右。(GBDCN, 2020)。水飞蓟宾（silbinin， SIL）是一种从水飞蓟中提取的黄烷脂素，具有很强的治疗潜力。本研究阐明了SIL对DEP后糖尿病大鼠胰腺葡萄糖调节通路（PI3K-AKT-GLUT 2和AMPK-GLUT 2）、炎症和氧化还原失衡的影响。用链脲佐菌素诱导大鼠2型糖尿病，经40 mg/kg的SIL处理后，DEP（0.4和0.5 mg/kg）进一步危害大鼠。为了进行比较，平行组的非糖尿病大鼠暴露于DEP，然后用SIL治疗，同时将结果与糖尿病组进行比较。结果表明，SIL导致胰岛素相关基因（PI3K， AKT， AMPK, GLUT 2），炎症标志物（IL-1β, IL-10），过氧化（MDA， CD）和抗氧化状态（SOD， CAT， GPX， GSH, HO-1）在体内被DEP和高血糖负诱导的显著/实质性调节，从而恢复葡萄糖稳态。综上所述，SIL提供了改善DEP和高血糖/血糖水平升高引起的胰腺毒性的潜力。

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引用次数: 0

Impact of eating duration on weight management, sleeping quality, and psychological stress: A pilot study 进食时间对体重管理、睡眠质量和心理压力的影响：一项初步研究。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-12-17 DOI: 10.1016/j.jnutbio.2024.109835

Li-Juan Tan , Sangah Shin

The daily eating window significantly impacts weight and metabolic health, yet its ideal duration remains uncertain. Thirty-four healthy middle-aged women were randomly assigned to two intervention groups: 8-h time-restricted eating (TRE) and 14-h time-extended eating (EXE). Each intervention lasted 4 wk, with a 16-d washout period before switching to the other intervention. Clinical biomarkers were collected before and after each intervention, and sleep quality was assessed using the Korean Version of the Pittsburgh Sleep Quality Index (PSQI-K). Additionally, a daily visual analogue scale (VAS) was used to evaluate psychological changes. The TRE group experienced significant weight reduction, lower fasting plasma glucose and total serum cholesterol levels compared to the EXE group, but with an increase in systolic blood pressure. The EXE group showed improved blood pressure. The TRE group reported higher stress levels on the VAS, but the PSQI-K indicated improved sleep quality during the second intervention. An 8-h TRE, without calorie restriction or diet composition changes, proves more beneficial for weight management and plasma glucose control compared to the 14-h EXE among Korean women. Implementation of this approach is recommended to be gradual to mitigate psychological fluctuations and adverse blood pressure changes.

The trial was registered with ClinicalTrials.gov (ID: NCT05964179) and Clinical Research Information Service (CRIS, Korea) (ID: KCT0008640).

背景：每日进食窗口期显著影响体重和代谢健康，但其理想持续时间仍不确定。方法：34名健康中年妇女随机分为8小时限时进食（TRE）和14小时延长进食（EXE）两组。每个干预持续4周，在切换到另一个干预之前有16天的洗脱期。在每次干预前后收集临床生物标志物，并使用韩国版匹兹堡睡眠质量指数（PSQI-K）评估睡眠质量。此外，每日视觉模拟量表（VAS）用于评估心理变化。结果：与EXE组相比，TRE组体重明显减轻，空腹血糖和血清总胆固醇水平降低，但收缩压升高。EXE组血压有所改善。TRE组在VAS上报告了更高的压力水平，但PSQI-K显示在第二次干预期间睡眠质量有所改善。结论：在韩国女性中，不限制卡路里或改变饮食成分的8小时TRE比14小时EXE更有利于体重管理和血糖控制。建议逐步实施这种方法，以减轻心理波动和不利的血压变化。

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引用次数: 0

Protective effects of Kaempferol on hepatic apoptosis via miR-26a-5p enhancement and regulation of TLR4/NF-κB and PKCδ in a rat model of nonalcoholic fatty liver 山奈酚通过增强miR-26a-5p和调节TLR4/NF-κB和PKCδ对非酒精性脂肪肝大鼠肝细胞凋亡的保护作用

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-12-17 DOI: 10.1016/j.jnutbio.2024.109833

Eman H. Basha , Islam Ibrahim Hegab , Radwa Ismail , Marwa Mohamed Atef , Omnia Safwat El-Deeb , Rowida Rafaat Ibrahim , Heba Bassiony Ghanem , Radwa Eissa , Marwa S. Taha , Shorouk E. Mwafy , Fatma H. Rizk , Ola M. Salem , Muhammad T. Abdel Ghafar , Yasser Mostafa Hafez , Shimaa Mashal , Manar Mohammed El Tabaa , Yasmeen M. El-Harty

This study aimed to evaluate kaempferol's, a dietary flavonoid widely present in plants, potential impact on nonalcoholic fatty liver disease (NAFLD) and its underlying mechanisms. In this study, 60 adult male rats were used and divided into a control group receiving a standard pellet diet, a kaempferol-treated group receiving kaempferol (250 mg/kg), a high-fat diet (HFD) group receiving HFD, and a kaempferol-treated HFD group. At the end of the experiment, the total lipid profile and liver enzymes were assayed in the serum. Additionally, oxidative stress (malondialdehyde and superoxide dismutase), inflammatory (tumor necrosis factor-alpha), apoptotic (caspase 3) markers, and nuclear factor-κB (NF-κB) and Toll-like receptor 4 (TLR4) concentrations were assayed in the liver tissues. Furthermore, miR-26a and PKCδ gene expression and beclin 1 immunohistochemical expression were determined in liver tissues. Our findings revealed that kaempferol significantly protects against the development of NAFLD in rats as well as inflammatory, oxidative, and apoptotic changes in their liver tissues by inhibiting PKCδ and the TLR-4/NF-κB signaling pathway while enhancing autophagy (Beclin 1 expression) via upregulating miR-26a expression. Accordingly, kaempferol holds promise as a complementary medication for the prevention of NAFLD. Nonetheless, more research is needed to fully understand its additional effects on liver tissue and to develop novel medications that activate miR-26a.

A link between lipid metabolic abnormalities and miRNAs was demonstrated as upregulating miR-26a-5p by kaempferol mitigates the inflammation, apoptosis, and disrupted autophagy via regulating TLR4/NF-κB pathway and PKC in NAFLD.

本研究旨在评估山奈酚（一种广泛存在于植物中的膳食类黄酮）对非酒精性脂肪性肝病（NAFLD）的潜在影响及其潜在机制。本研究选用成年雄性大鼠60只，分为标准颗粒饮食对照组、山奈酚处理组（山奈酚250 mg/kg）、高脂饮食组（HFD）和山奈酚处理HFD组。实验结束时，测定血清总脂质谱和肝酶。此外，检测肝组织中氧化应激（丙二醛和超氧化物歧化酶）、炎症（肿瘤坏死因子- α）、凋亡（caspase 3）标志物、核因子-κB （NF-κB）和toll样受体4 （TLR4）浓度。进一步检测miR-26a、PKCδ基因表达及beclin 1免疫组化表达在肝组织中的表达。我们的研究结果表明，山奈酚通过抑制PKCδ和TLR-4/NF-κB信号通路，同时通过上调miR-26a表达增强自噬（Beclin 1表达），显著保护大鼠NAFLD的发展以及肝组织的炎症、氧化和凋亡变化。因此，山奈酚有望成为预防NAFLD的补充药物。然而，需要更多的研究来充分了解其对肝组织的额外影响，并开发激活miR-26a的新型药物。新的和值得关注的是：山奈酚上调miR-26a-5p通过调节TLR4/NF-κB通路和PKC减轻NAFLD的炎症、凋亡和自噬中断，证明了脂质代谢异常与miRNAs之间的联系。

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引用次数: 0

Cyanidin-3-rutinoside from Mori Fructus ameliorates dyslipidemia via modulating gut microbiota and lipid metabolism pathway 桑子花青素-3-芦丁苷通过调节肠道菌群和脂质代谢途径改善血脂异常。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-12-16 DOI: 10.1016/j.jnutbio.2024.109834

Shi Zhong , Ya-Nan Yang , Jin-Xi Huo , Yu-Qing Sun , Hui Zhao , Xin-Tian Dong , Jia-Yi Feng , Jin Zhao , Chong-Ming Wu , You-Gui Li

Dyslipidemia is responsible for pathologies of cardiovascular diseases and gut microbiota plays an essential role in lipid metabolism. Dietary supplementation is an important supplement to medicine in management of dyslipidemia. Mori Fructus is a popular Asia medical food with various pharmacological benefits including anti-hyperlipidemia. Cyanidin-3-rutinoside (C3R) is the main anthocyanin component in Mori Fructus, but the lipid-lowering effect and underlying mechanism of Mori Fructus-derived C3R remains unknown. In this study, we assessed the beneficial effect of Mori Fructus-derived C3R in HFD-induced hyperlipidemic mice and investigated its potential mechanism through 16S rRNA-based metagenomics and transcriptomics analysis. Our results showed that C3R from Mori Fructus significantly decreased serum lipid levels and attenuated hepatic damage induced by HFD. Analysis of the gut microbiota revealed that C3R altered the specific gut micorbiota but not changed its diversity. Among changed genera, Family_XIII_UCG-001 was significantly enriched by C3R, and it was positively associated with HDL-c, but negatively related with TC, TG, LDL-c, insulin and body weight. Transcriptomic analysis showed that C3R activates the lipid metabolism related pathways including MAPK signaling pathway, Rap1 signaling pathway, Ras signaling pathway and PI3K-Akt signaling pathway. Additionally, correlation analysis unraveled that C3R-enriched Family_XIII_UCG-001 was negatively associated with C3R-inhibited genes of Camk2a, Eef1a2, Gad1, Kif5a and Sv2b, which further positively related with TC, TG, LDL-c, insulin and body weight, but negatively associated with HDL-c. In sum, C3R may inhibit expression of immune-related genes by enriching the Family_XIII_UCG-001 genus, further ameliorating lipid metabolism disorders in HFD-challenged mice. This study provides an optional strategy for the daily management of dyslipidemia.

血脂异常与心血管疾病的病理有关，肠道微生物群在脂质代谢中起着至关重要的作用。膳食补充是治疗血脂异常的重要药物补充。桑子是一种受欢迎的亚洲医疗食品，具有多种药理作用，包括抗高脂血症。花青素-3-芦丁苷（Cyanidin-3-rutinoside, C3R）是桑子花青素的主要成分，但其降脂作用及其机制尚不清楚。在本研究中，我们通过基于16S rrna的宏基因组学和转录组学分析，评估了桑子衍生的C3R对hfd诱导的高脂血症小鼠的有益作用，并探讨了其潜在机制。结果表明，桑子C3R可显著降低血清脂质水平，减轻HFD引起的肝损伤。肠道菌群分析显示，C3R改变了特定的肠道菌群，但没有改变其多样性。在改变属中，Family_XIII_UCG-001被C3R显著富集，与HDL-c呈正相关，与TC、TG、LDL-c、胰岛素、体重呈负相关。转录组学分析显示，C3R激活脂质代谢相关通路，包括MAPK信号通路、Rap1信号通路、Ras信号通路和PI3K-Akt信号通路。此外，相关分析显示，c3r富集的Family_XIII_UCG-001与Camk2a、Eef1a2、Gad1、Kif5a、Sv2b等c3r抑制基因呈负相关，与TC、TG、LDL-c、胰岛素、体重呈正相关，与HDL-c呈负相关。综上所述，C3R可能通过富集Family_XIII_UCG-001属抑制免疫相关基因的表达，进一步改善手足口病小鼠脂质代谢紊乱。本研究为血脂异常的日常管理提供了一种可选的策略。

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引用次数: 0

EPA but not DHA prevents lipid metabolism disorders by regulating myogenic IL-6 in high-fat fed mice EPA而非DHA通过调节肌源性IL-6阻止高脂喂养小鼠脂质代谢紊乱。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-12-09 DOI: 10.1016/j.jnutbio.2024.109815

Qunying Xie , Lianzhi Mao , Ning Xiong, Qiting Cheng, Wei Tang, Ci Li, Chongxiang Zeng, Zhilin Liu, Limei Mao

Lipid metabolism disorder serve as a critical starting point for the development of chronic non-communicable diseases (NCDs). Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) are known for their lipid-lowering properties, but few studies have revealed their differences from the perspective of skeletal muscle endocrinology. Myogenic IL-6 has garnered significant attention for its role in energy distribution. The primary aim of this study was to investigate the effects and mechanisms of EPA and DHA on myogenic IL-6 and lipid metabolism disorders in mice, and to clarify the association between the alleviation of lipid metabolism disorders and myogenic IL-6 mediated by EPA/DHA. We found that EPA and DHA not only prevented high-fat diet-induced lipid metabolism disorders, but also up-regulated the expression of myogenic IL-6 by activating TRPV1/Ca²⁺ signaling in skeletal muscle. However, the lipid metabolism prevention effect mediated by EPA was weakened after knockout gene of myogenic IL-6, with its body weight and body fat increased and a large amounts of lipid deposited in the blood, liver, and adipocytes. Meanwhile, there no significantly differences of AMPK/STAT3 signaling in adipose tissue between groups after knockout gene of myogenic IL-6. Based on the results above, we concluded that EPA and DHA can stimulate the production of myogenic IL-6 through TRPV1/Ca²⁺ signaling in skeletal muscle. The prevention effect of lipid metabolism disorders by EPA, but not DHA, relies on myogenic IL-6, with the underlying mechanism may involving the enhancement of AMPK/STAT3 signaling mediated by myogenic IL-6 in adipose tissues.

脂质代谢紊乱是慢性非传染性疾病发展的一个关键起点。二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）以其降脂特性而闻名，但很少有研究从骨骼肌内分泌学的角度揭示它们的差异。肌源性IL-6因其在能量分布中的作用而受到广泛关注。本研究的主要目的是探讨EPA和DHA对小鼠肌源性IL-6和脂质代谢紊乱的影响及其机制，阐明EPA/DHA介导的脂质代谢紊乱的缓解与肌源性IL-6之间的关系。我们发现EPA和DHA不仅可以预防高脂肪饮食引起的脂质代谢紊乱，还可以通过激活骨骼肌中的TRPV1/Ca2+信号来上调肌源性IL-6的表达。而敲除肌源性IL-6基因后，EPA介导的脂质代谢预防作用减弱，其体重和体脂增加，大量脂质沉积在血液、肝脏和脂肪细胞中。同时，敲除肌源性IL-6基因后，各组脂肪组织AMPK/STAT3信号无显著差异。基于以上结果，我们认为EPA和DHA可以通过骨骼肌中TRPV1/Ca2+信号通路刺激肌源性IL-6的产生。EPA而非DHA对脂质代谢紊乱的预防作用依赖于肌源性IL-6，其潜在机制可能与肌源性IL-6介导的脂肪组织中AMPK/STAT3信号的增强有关。

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引用次数: 0