Journal of Nutritional Biochemistry最新文献_第3页

Behavioral changes and transcriptional regulation of mesolimbic dopaminergic genes in a mouse model of binge eating disorder by diet intermittent access 饮食间歇性接触暴饮暴食症小鼠模型的行为变化和间叶多巴胺能基因的转录调控。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-18 DOI: 10.1016/j.jnutbio.2024.109784

Renato Elias Moreira Júnior , Agatha Sondertoft Braga Pedersen , Raquel Mary Ferreira , Guilherme Henrique de Asevedo , Grazielle Laudares Mendes , Karine Ribeiro , Tatiani Uceli Maioli , Ana Maria Caetano de Faria , Ana Lúcia Brunialti-Godard

Binge Eating Disorder (BED) is among the most prevalent eating disorders worldwide. It is characterized by recurrent episodes of excessive consumption of palatable foods in short periods, accompanied by a sense of loss of control and distress around the episode, which tends to worsen over time. The mesolimbic dopaminergic system influences on reinforcement and reward-seeking behaviors is implicated in the disorder's pathogenesis. Animal models that replicate the clinical conditions observed in humans, including the disorder progression, are essential for understanding the underlying physiological mechanisms of BED. This study aimed to evaluate binge eating behavior induced by intermittent High Sugar and Butter (HSB) diet access in mice, their phenotypes, transcriptional regulation of mesolimbic dopaminergic system genes, and behavior. Thus, mice were subdivided into three groups: CHOW (maintenance diet only), HSB-i (maintenance diet with thrice-weekly access to HSB), and HSB (continuous access to HSB). Animals were subjected to marble-burying and light-dark box behavioral tests, and transcriptional regulation was evaluated by RT-qPCR. The results indicated that the HSB-i group established a feeding pattern of significantly more kilocalories on days when HSB was available and reduced intake on non-HSB days similar to human binge eating. Over time, binge episodes intensified, potentially indicating a tolerance effect. Additionally, these animals behave differently towards preferring the HSB diet and exhibited altered transcriptional regulation of the Drd1, Slc6a3, and Lrrk2 genes. Our study provides a mouse model that reflects human BED, showing a progression in binge episodes and mesolimbic dopamine pathway involvement, suggesting targets for future therapeutic interventions.

暴饮暴食症（BED）是全球最普遍的饮食失调症之一。它的特点是反复发作，在短期内摄入过多适口食物，并伴有失控感和围绕发作的痛苦，这种情况往往会随着时间的推移而恶化。中边缘多巴胺能系统对强化和寻求奖赏行为的影响与该疾病的发病机制有关。复制人类临床症状（包括疾病进展）的动物模型对于了解暴食症的潜在生理机制至关重要。本研究旨在评估小鼠间歇性摄入高糖高黄油（HSB）饮食诱发的暴食行为、其表型、间叶多巴胺能系统基因的转录调控以及行为。因此，小鼠被细分为三组：CHOW（仅摄入维持性饮食）、HSB-i（摄入维持性饮食，每周三次摄入 HSB）和 HSB（持续摄入 HSB）。对动物进行埋大理石和光-暗箱行为测试，并通过 RT-qPCR 评估转录调控。结果表明，HSB-i 组建立了一种进食模式，即在有 HSB 的日子里摄入的热量显著增加，而在没有 HSB 的日子里摄入的热量则减少，这与人类的暴饮暴食类似。随着时间的推移，暴食现象会加剧，这可能表明存在耐受效应。此外，这些动物对 HSB 饮食的偏好表现不同，并表现出 Drd1、Slc6a3 和 Lrrk2 基因转录调控的改变。我们的研究提供了一个反映人类暴饮暴食症的小鼠模型，显示了暴饮暴食发作的进展和间叶多巴胺通路的参与，为未来的治疗干预提出了目标。

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引用次数: 0

Tsg101 knockout in the mammary gland leads to a decrease in small extracellular vesicles in milk from C57BL/6J dams and contributes to leakiness of the gut mucosa and reduced postnatal weight gain in suckling pups 乳腺中的Tsg101基因敲除会导致C57BL/6J母鼠乳汁中的小细胞外囊泡减少，并导致肠道粘膜渗漏和哺乳幼鼠出生后体重增加减少。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-17 DOI: 10.1016/j.jnutbio.2024.109782

Javaria Munir , Mahrou Sadri , Janos Zempleni

Human milk contains 2.2 ± 1.5×10¹¹ small extracellular vesicles (sEVs) per milliliter and human infants consume 1.7×10¹⁴ milk sEVs (sMEVs) daily in 800 mL milk. Infant formula contains trace amounts of sMEVs. To date, eight adverse effects of milk depletion and five beneficial effects of sMEV supplementation have been reported including studies in infants and neonate mice. Formula-fed infants do not realize the benefits of sMEVs. Most of the phenotyping studies reported to date have the limitation that sMEV depletion and supplementation were initiated after mice were weaned. Here, we used a genetics approach for assessing effects of sMEV depletion on the development of suckling mice. Newborn C57BL/6J pups were fostered to Tumor Susceptibility Gene 101 (Tsg101) mammary-specific knockout (KO) dams or C57BL/6J dams (controls) in synchronized pregnancies. Tsg101 KO was associated with an 80% decrease of sMEVs. Postnatal weight gain and gut health (histology, morphology, and barrier function) were assessed until weaning at age three weeks. We observed a significant decrease in weight gain, length of small intestine, villi height, crypt depth, and intestinal barrier function in male and female pups fostered to Tsg101 dams compared to pups fostered to control dams. The effect size varied between 11 and 32 percent. Maternal Tsg101 KO did not affect the dams’ health, content of macronutrients and dry mass of milk and had no effect on the amount of milk consumed by pups. We conclude that sMEVs are important for growth and gut health in neonate mice.

母乳中每毫升含有 2.2 ± 1.5×1011 个细胞外小泡 (sEV)，800 毫升母乳中婴儿每天摄入 1.7×1014 个牛奶小泡 (sMEV)。婴儿配方奶粉中含有微量的 sMEVs。迄今为止，已有八项关于牛奶消耗的不良影响和五项关于补充 sMEV 的有益影响的报道，其中包括对婴儿和新生小鼠的研究。配方奶喂养的婴儿并不能从 sMEVs 中获益。迄今为止报道的大多数表型研究都有一个局限性，即小鼠断奶后才开始消耗和补充 sMEV。在此，我们采用遗传学方法来评估sMEV消耗对哺乳小鼠发育的影响。新生 C57BL/6J 幼鼠由肿瘤易感基因 101（Tsg101）乳腺特异性基因敲除（KO）母鼠或 C57BL/6J 母鼠（对照组）同步哺育。Tsg101 KO与sMEVs减少80%有关。对出生后体重增加和肠道健康（组织学、形态学和屏障功能）进行了评估，直到三周大时断奶。我们观察到，与对照组母鼠的幼崽相比，Tsg101母鼠寄养的雄性和雌性幼崽的体重增加、小肠长度、绒毛高度、隐窝深度和肠道屏障功能都明显下降。效应大小在 11% 到 32% 之间。母体 Tsg101 KO 不会影响母体的健康、宏量营养素含量和干奶质量，也不会影响幼崽的吃奶量。我们的结论是，sMEVs 对新生小鼠的生长和肠道健康非常重要。

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引用次数: 0

Preventive and therapeutic effects of molecular iodine in a model of diabetes mellitus induced by streptozotocin 分子碘在链脲佐菌素诱导的糖尿病模型中的预防和治疗作用：针对葡萄糖变化的碘疗法。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-16 DOI: 10.1016/j.jnutbio.2024.109783

Julia Rodríguez-Castelán , Evangelina Delgado-González , Mónica Sánchez-Tapia , Brenda Anguiano , Nimbe Torres , Carmen Aceves

Diabetes mellitus (DM) is a multifactorial condition that involves oxidative alterations and dysbiosis of the gut microbiota associated with an imbalance in glucose metabolism. Therefore, the need to develop integrative therapies that are both effective and have fewer side effects has become evident in recent years. Molecular iodine (I₂) has antioxidant effects in preclinical hyperglycemic models. The present work analyzes the preventive and therapeutic effects of oral I₂ supplementation in a DM model induced by low doses of streptozotocin (STZ). Male CD1 mice (12 weeks old) were divided into the following groups: control, STZ (20 mg/kg/day, i.p., for 5 days), I₂ (0.2 mg/Kg in drinking water), preventive (STZ + I₂), and therapeutic (I₂ supplementation from day 35 to day 90; STZ + I_2(Ther)). The supplementation with I₂ prevented and normalized hyperglycemia, hypercholesterolemia, and hypertriglyceridemia associated with STZ, preserving pancreatic, liver, muscle, and adipose tissue morphology and normalizing inflammatory gene induction (TLR2, TLR4, NFkβ, TNFα) in several tissues. Furthermore, compared to the STZ group, the presence of I₂ favored a more significant abundance of beneficial bacteria that support the integrity of the intestinal epithelial barrier and higher α-diversity. In conclusion, the I₂ supplement has preventive and therapeutic effects, reducing oxidative damage and reestablishing microbiota diversity following STZ exposure.

糖尿病（DM）是一种多因素疾病，涉及与葡萄糖代谢失衡相关的氧化改变和微生物群失调。因此，近年来，开发有效且副作用较少的综合疗法的需求已变得十分明显。分子碘（I2）在临床前高血糖模型中具有抗氧化作用。本研究分析了在低剂量链脲佐菌素（STZ）诱导的糖尿病模型中口服碘2的预防和治疗作用。雄性 CD1 小鼠（12 周大）被分为以下几组：对照组、STZ 组（20 毫克/千克/天，静脉注射，连续五天）、I2 组（0.2 毫克/千克，加入饮用水中）、预防组（STZ + I2）和治疗组（从第 35 天到第 90 天补充 I2；STZ + I2(Ther)）。补充 I2 可预防 STZ 引起的高血糖、高胆固醇血症和高甘油三酯血症，并使之恢复正常，还能保护胰腺、肝脏、肌肉和脂肪组织的形态，并使多个组织的炎症基因诱导（TLR2、TLR4、NFkβ、TNFα）恢复正常。此外，与 STZ 组相比，I2 的存在有利于增加有益菌的数量，从而支持肠上皮屏障的完整性和更高的α-多样性。总之，在接触 STZ 后，I2 补充剂具有预防和治疗作用，可减少氧化损伤并重建微生物群的多样性。

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引用次数: 0

Inhibition of selenium supply function of selenoprotein p through adduct formation by sulforaphane 红豆杉通过加合物形成抑制硒蛋白 P 的供硒功能

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-16 DOI: 10.1016/j.jnutbio.2024.109781

Xinying Ye , Takashi Toyama , Wang Yinuo, Runa Kudo, Siu Stephanie, Kotoko Arisawa, Yoshiro Saito

Selenium is a potent nucleophile essential for selenoenzymes, such as glutathione peroxidase (also known as GSH-Px; GPX; GPx) and selenoprotein P (also known as SelP; SEPP1; SELENOP; SeP). SeP is predominantly secreted from the liver and functions as a selenium carrier in plasma. We previously found that sulforaphane (SFN), an electrophilic phytochemical, reduces SeP production in cultured hepatocytes and mouse liver, however, the effect of electrophilic modification of SeP by SFN on selenium transport and metabolism remains unclear. In the present study, we demonstrate that sulforaphane covalently modifies selenocysteine/cysteine residues of SeP using an acidic biotin PAEC₅ maleimide labeling assay, which allows for focused-labeling of selenocysteine residues. Although the SFN-SeP adduct can be taken up by HepG2 cells and degraded by the lysosome, it was less effective in inducing GPx expression. Our findings indicate that SFN disrupts the selenium supply pathway through the formation of the SeP-SFN adduct.

硒是一种强效亲核素，是谷胱甘肽过氧化物酶（又称 GSH-Px；GPX；GPx）和硒蛋白 P（又称 SelP；SEPP1；SELENOP；SeP）等硒酶所必需的。SeP 主要从肝脏分泌，在血浆中起硒载体的作用。我们之前发现，亲电植物化学物质 sulforaphane 可减少培养肝细胞和小鼠肝脏中 SeP 的产生，但 SFN 对 SeP 的亲电修饰对硒转运和代谢的影响仍不清楚。在本研究中，我们利用酸性生物素 PAEC5 马来酰亚胺标记法对硒代半胱氨酸残基进行了集中标记，结果表明苏拉环能共价修饰 SeP 的硒代半胱氨酸/半胱氨酸残基。虽然 SFN-SeP 加合物能被 HepG2 细胞吸收并被溶酶体降解，但它在诱导 GPx 表达方面的效果较差。我们的研究结果表明，SFN 通过形成 SeP-SFN 加合物破坏了硒的供应途径。

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引用次数: 0

Luteolin alleviates muscle atrophy, mitochondrial dysfunction and abnormal FNDC5 expression in high fat diet-induced obese rats and palmitic acid-treated C2C12 myotubes 木犀草素能缓解高脂饮食诱导的肥胖大鼠和棕榈酸处理的 C2C12 肌细胞的肌肉萎缩、线粒体功能障碍和 FNDC5 表达异常。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-11 DOI: 10.1016/j.jnutbio.2024.109780

Yiyuan Zhang, Chunyun Luo, Puxin Huang, Yahong Cheng, Yufang Ma, Jiefang Gao, Hong Ding

Obesity is associated with a series of skeletal muscle impairments and dysfunctions, which are characterized by metabolic disturbances and muscle atrophy. Luteolin is a phenolic phytochemical with broad pharmacological activities. The present study aimed to evaluate the protective effects of Luteolin on muscle function and explore the potential mechanisms in high-fat diet (HFD)-induced obese rats and palmitic acid (PA)-treated C2C12 myotubes. Male Sprague-Dawley (SD) rats were fed with a control diet or HFD and orally administrated 0.5% sodium carboxymethyl cellulose (vehicle) or Luteolin (25, 50, and 100 mg/kg, respectively) for 12 weeks. The results showed that Luteolin ameliorated HFD-induced body weight gain, glucose intolerance and hyperlipidemia. Luteolin also alleviated muscle atrophy, decreased ectopic lipid deposition and prompted muscle-fiber-type conversion in the skeletal muscle. Meanwhile, we observed an evident improvement in mitochondrial quality control and respiratory capacity, accompanied by reduced oxidative stress. Mechanistic studies indicated that AMPK/SIRT1/PGC-1α signaling pathway plays a key role in the protective effects of Luteolin on skeletal muscle in the obese states, which was further verified by using specific inhibitors of AMPK and SIRT1. Moreover, the mRNA expression levels of markers in brown adipocyte formation were significantly up-regulated post Luteolin supplementation in different adipose depots. Taken together, these results revealed that Luteolin supplementation might be a promising strategy to prevent obesity-induced loss of mass and biological dysfunctions of skeletal muscle.

肥胖与一系列骨骼肌损伤和功能障碍有关，其特点是代谢紊乱和肌肉萎缩。木犀草素是一种酚类植物化学物质，具有广泛的药理活性。本研究旨在评估木犀草素对高脂饮食（HFD）诱导的肥胖大鼠和棕榈酸（PA）处理的 C2C12 肌管肌肉功能的保护作用，并探索其潜在机制。雄性斯普拉格-道利（SD）大鼠以对照组饮食或高脂饮食喂养，并口服 0.5% 羧甲基纤维素钠（载体）或木犀草素（分别为 25、50 和 100 mg/kg）12 周。结果表明，木犀草素可改善高纤维食物诱导的体重增加、糖耐量减低和高脂血症。木犀草素还能缓解肌肉萎缩，减少异位脂质沉积，促进骨骼肌肌纤维型转化。同时，我们观察到线粒体质量控制和呼吸能力得到明显改善，氧化应激也有所降低。机理研究表明，在木犀草素对肥胖状态下骨骼肌的保护作用中，AMPK/SIRT1/PGC-1α 信号通路起着关键作用。此外，补充叶黄素后，棕色脂肪细胞形成标志物的 mRNA 表达水平在不同脂肪贮备中均显著上调。综上所述，这些结果表明，补充木犀草素可能是预防肥胖引起的骨骼肌质量下降和生物功能障碍的一种有效策略。

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引用次数: 0

Serum selenium, selenoprotein P and glutathione peroxidase 3 in rheumatoid, psoriatic, juvenile idiopathic arthritis, and osteoarthritis 类风湿、银屑病、幼年特发性关节炎和骨关节炎患者的血清硒、硒蛋白 P 和谷胱甘肽过氧化物酶 3。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-09 DOI: 10.1016/j.jnutbio.2024.109776

Lukas Wahl , Thilo Samson Chillon , Petra Seemann , Sarah Ohrndorf , Ragna Ochwadt , Wolfgang Becker , Lutz Schomburg , Paula Hoff

Selenoprotein P (SELENOP) controls selenium (Se) transport, and glutathione peroxidase 3 (GPx3) elicits antioxidant activity in blood. Inflammation associates with Se deficiency, but knowledge concerning selenoproteins in inflammatory rheumatic musculoskeletal diseases (iRMD) is limited. We compared three Se biomarkers in patients with rheumatoid (RA), psoriatic (PsA), and juvenile idiopathic arthritis (JIA) in comparison to osteoarthritis (OA) and healthy subjects, to improve the data base on selenoprotein expression in iRMD.

The cross-sectional study enrolled n=272 patients with RA (n=131), PsA (n=67), JIA (n=22) and OA (n=52). Serum Se was quantified by total reflection X-ray fluorescence, SELENOP by ELISA and GPx3 by an enzymatic test. Data from the EPIC trial served as reference. Impairment of daily life was assessed by the Functional Ability Questionnaire (FfbH).

Serum SELENOP and Se concentrations correlated linearly in all groups and were below the average measured in EPIC. Se concentration was not different between the patient groups. Compared to controls, SELENOP levels were low in iRMD patients. GPx3 activity was particularly low in JIA and PsA. Seropositive but not seronegative RA patients displayed a disrupted interaction between GPx3 and Se or SELENOP. SELENOP associated with the functional status measured by the FfbH, most pronounced in OA (R=0.76, P < .01).

The data indicate selenoprotein deficiency in the majority of patients with iRMD, and a positive relation of SELENOP with functional status in OA. Since increased Se supply improves selenoprotein biosynthesis, a personalized correction of diagnosed deficiency merits consideration to improve Se transport and ameliorate disease burden.

简介硒蛋白 P (SELENOP) 控制硒的运输，谷胱甘肽过氧化物酶 3 (GPx3) 在血液中激发抗氧化活性。炎症与硒缺乏有关，但有关炎症性风湿性肌肉骨骼疾病（iRMD）中硒蛋白的知识却很有限。我们比较了类风湿（RA）、银屑病（PsA）和幼年特发性关节炎（JIA）患者与骨关节炎（OA）和健康人的三种硒生物标志物，以完善 iRMD 中硒蛋白表达的数据基础：这项横断面研究共招募了272名RA（131人）、PsA（67人）、JIA（22人）和OA（52人）患者。血清中的硒通过全反射X射线荧光法进行定量，SELENOP通过酶联免疫吸附法进行定量，GPx3通过酶法测试进行定量。EPIC 试验的数据作为参考。日常生活障碍通过功能能力问卷（FfbH）进行评估：结果：在所有组别中，血清 SELENOP 和 Se 浓度呈线性相关，均低于 EPIC 试验中测得的平均值。不同患者组之间的硒浓度没有差异。与对照组相比，iRMD 患者的 SELENOP 水平较低。JIA和PsA患者的GPx3活性特别低。血清反应阳性的 RA 患者与血清反应阴性的 RA 患者之间的 GPx3 与 Se 或 SELENOP 之间的相互作用被破坏。SELENOP与FfbH测量的功能状态相关，在OA中最为明显（R=0.76，p讨论：数据表明，大多数 iRMD 患者缺乏硒蛋白，而 SELENOP 与 OA 的功能状态呈正相关。由于增加 Se 的供应可改善硒蛋白的生物合成，因此值得考虑对诊断出的缺乏症进行个性化矫正，以改善 Se 的转运并减轻疾病负担。

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引用次数: 0

Astaxanthin improves lipotoxicity, lipid peroxidation and oxidative stress in kidney of sucrose-rich diet-fed rats 虾青素可改善富含蔗糖饮食大鼠肾脏的脂毒性、脂质过氧化和氧化应激。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-05 DOI: 10.1016/j.jnutbio.2024.109779

Michelle Berenice Vega Joubert , Paola Inés Ingaramo , Pablo Collins , María Eugenia D'Alessandro

Metabolic Syndrome (MS) is a cluster of metabolic risk factors, characterized by abdominal obesity, dyslipidemia, hypertension, insulin resistance, among others. The purpose of the study was to evaluate the astaxanthin (AXT) effects extracted from freshwater crab (Dilocarcinus pagei) at the Paraná Basin on lipotoxicity, lipid peroxidation and oxidative stress in the kidney of rats fed with a sucrose-rich diet (SRD). We hypothesized that daily administration of AXT prevents kidney damage by reducing lipotoxicity, lipid peroxidation, and reactive oxygen species (ROS), and by improving antioxidant enzyme defenses and crosstalk between NrF2 and NF-ĸB transcription factors. Male Wistar rats were fed a reference diet (RD), RD+AXT, SRD and SRD+AXT (AXT daily oral dose: [10 mg/kg body weight]) for 90 days. Systolic and diastolic blood pressure, biochemical assays in serum and urine were evaluated. Renal cortex samples were taken for histological analysis, determination of triglyceride content, ROS, thiobarbituric acid reactive substances (TBARS), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) enzyme activities and glutathione content (GSH). 4-HNE, NrF2, and NF-ĸB p65 expression were analyzed by immunohistochemistry. We demonstrated that daily oral supplementation of AXT to animals fed a SRD reduced systolic and diastolic blood pressure, histological renal damage, lipid accumulation, ROS and lipid peroxidation, and increased CAT and GPx activities. NrF2 protein expression in renal cortex was increased, whilst NF-ĸB p65 was reduced. AXT extracted from freshwater crabs (Dilocarcinus pagei) may be promising nutritional strategy for the prevention of renal alterations present in this model.

代谢综合征（MS）是一组代谢风险因素，以腹部肥胖、血脂异常、高血压、胰岛素抵抗等为特征。本研究旨在评估从巴拉那盆地淡水蟹（Dilocarcinus pagei）中提取的虾青素（AXT）对富含蔗糖饮食（SRD）的大鼠肾脏的脂毒性、脂质过氧化和氧化应激的影响。我们假设，每天服用 AXT 可降低脂毒性、脂质过氧化和活性氧（ROS），改善抗氧化酶的防御能力以及 NrF2 和 NF-ĸB 转录因子之间的串扰，从而防止肾脏损伤。给雄性 Wistar 大鼠喂食参考饮食 (RD)、RD+AXT、SRD 和 SRD+AXT [AXT 每日口服剂量：（10 毫克/千克体重）] 90 天。对收缩压和舒张压、血清和尿液中的生化指标进行了评估。取肾皮质样本进行组织学分析，测定甘油三酯含量、ROS、硫代巴比妥酸活性物质（TBARS）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）的酶活性和谷胱甘肽含量（GSH）。免疫组化法分析了 4-HNE、NrF2 和 NF-ĸB p65 的表达。我们的研究表明，每天口服 AXT 可降低以 SRD 为食的动物的收缩压和舒张压、组织学肾损伤、脂质积累、ROS 和脂质过氧化反应，并提高 CAT 和 GPx 活性。肾皮质中 NrF2 蛋白表达增加，NF-ĸB p65 减少。从淡水蟹（Dilocarcinus pagei）中提取的 AXT 可能是预防该模型中出现的肾脏改变的一种有前景的营养策略。

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引用次数: 0

Lycopene attenuates D-galactose-induced memory and behavioral deficits by mediating microbiota-SCFAs-gut-brain axis balance in female CD-1 mice 番茄红素通过调节雌性CD-1小鼠体内微生物群-SCFAs-肠脑轴的平衡，减轻D-半乳糖诱导的记忆和行为缺陷。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-05 DOI: 10.1016/j.jnutbio.2024.109777

Jia Wang , Yuqi Shen , Lu Li , Li Li , Juan Zhang , Mengling Li , Fubin Qiu

Aging impairs cognitive function, whereas nutritional intervention can delay aging and age-related diseases. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, the effects of LYC on memory and behavioral deficits induced by D-galactose (D-gal) treatment and the relative contribution of LYC-derived gut microbiota in these process were investigated. Results demonstrated that LYC showed effective protection on D-gal induced cognitive deficit and neuronal damage. Moreover, LYC treatment has beneficial effects on gut barrier damage, microbiota dysbiosis and levels of SCFAs in D-gal-induced subacute aging mice. Next, fecal microbiota transplantation (FMT) experiment was performed and increased SCFAs were observed in mice received stools from D-gal+LYC group when compared with D-gal-FMT group. Thus, we added SCFAs treatment served as a control group in order to evaluated whether the alterations of gut-brain axis could be attributed to LYC-reshaped gut microbiota and SCFAs. Results showed that recipient mice received SCFAs and stools from D-gal+LYC group have similar beneficial effects in improving gut and brain function, demonstrated as: improved intestinal health via elevating antioxidant enzymes contents, increasing the expressions of tight junctions proteins and protecting gut barrier, enhanced mice working memory capacity via alleviating hippocampal neurons impairment, improving synaptic function and enhancing mitochondrial function in the intestinal pseudo-aseptic mice. In conclusion, our results demonstrated that LYC-derived microbiome played a pivotal role in the regulation of cognitive functions during aging and enhanced SCFAs formation might be an important signaling molecule connecting gut microbiome and brain.

衰老会损害认知功能，而营养干预可以延缓衰老和与衰老相关的疾病。番茄红素（LYC）是一种天然类胡萝卜素，具有多种促进健康的特性，包括神经保护功能。本文研究了番茄红素对D-半乳糖（D-gal）处理诱导的记忆和行为缺陷的影响，以及番茄红素衍生的肠道微生物群在这些过程中的相对贡献。结果表明，LYC 能有效保护 D-gal 诱导的认知缺陷和神经元损伤。此外，LYC治疗对D-gal诱导的亚急性衰老小鼠的肠道屏障损伤、微生物群失调和SCFAs水平也有益处。接下来，我们进行了粪便微生物群移植（FMT）实验，结果发现与 D-gal-FMT 组相比，D-gal+LYC 组小鼠粪便中的 SCFAs 增加了。因此，我们添加了 SCFAs 处理作为对照组，以评估肠脑轴的改变是否可归因于 LYC 重组的肠道微生物群和 SCFAs。结果表明，接受 SCFAs 和 D-gal+LYC 组粪便的小鼠在改善肠道和大脑功能方面具有相似的益处，表现为：通过提高抗氧化酶含量、增加紧密连接蛋白的表达和保护肠道屏障来改善肠道健康；通过减轻海马神经元损伤、改善突触功能和增强线粒体功能来提高肠道假性变性小鼠的工作记忆能力。总之，我们的研究结果表明，LYC 衍生的微生物组在衰老过程中对认知功能的调控起着关键作用，而增强 SCFAs 的形成可能是连接肠道微生物组和大脑的重要信号分子。

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引用次数: 0

TGF-β2, EGF and FGF21 influence the suckling rat intestinal maturation TGF-β2、EGF 和 FGF21 对乳鼠肠道成熟的影响

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-05 DOI: 10.1016/j.jnutbio.2024.109778

Blanca Grases-Pintó , Paulina Torres-Castro , Mar Abril-Gil , Margarida Castell , María J. Rodríguez-Lagunas , Francisco J. Pérez-Cano , Àngels Franch

Some of the growth factors present in breast milk, such as transforming growth factor-β (TGF-β), epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), play important roles in the development of the intestinal tract. The aim of this study was to determine the effect of a supplementation with TGF-β2, EGF and FGF21 on suckling rats intestinal maturation. For this purpose, Wistar rats were supplemented daily with TGF-β2, EGF or FGF21 throughout the suckling period. We evaluated the functionality of the intestinal epithelial barrier through an in vivo dextran permeability assay, and by a histomorphometric and immunohistochemical study. In addition, the intestinal gene expression of tight junction-associated proteins, mucins, toll-like receptors, and maturation markers was analyzed. Moreover, the intraepithelial lymphocyte (IEL) phenotypical composition was established. During the suckling period, the supplementation with TGF-β2, EGF and FGF21 showed important signs of intestinal maturation. These results suggest that these molecules, present in breast milk, play a modulatory role in the maturation of the intestinal barrier function and the IEL composition during the suckling period.

母乳中的一些生长因子，如转化生长因子-β（TGF-β）、表皮生长因子（EGF）和成纤维细胞生长因子 21（FGF21），在肠道发育中发挥着重要作用。本研究旨在确定补充 TGF-β2、EGF 和 FGF21 对乳鼠肠道成熟的影响。为此，我们在 Wistar 大鼠的整个哺乳期每天为其补充 TGF-β2、EGF 或 FGF21。我们通过体内葡聚糖渗透性试验以及组织形态学和免疫组化研究评估了肠上皮屏障的功能。此外，还分析了肠道紧密连接相关蛋白、粘蛋白、收费样受体和成熟标志物的基因表达。此外，还确定了上皮内淋巴细胞（IEL）的表型组成。在哺乳期，补充 TGF-β2、EGF 和 FGF21 可显示肠道成熟的重要迹象。这些结果表明，母乳中的这些分子对哺乳期肠道屏障功能和IEL组成的成熟起着调节作用。

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引用次数: 0

In vivo and in silico insights into the antidiabetic efficacy of EVOO and hydroxytyrosol in a rat model 对 EVOO 和羟基酪醇在大鼠模型中抗糖尿病功效的体内和硅学洞察。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-05 DOI: 10.1016/j.jnutbio.2024.109775

Mahmoud Gamal , Mohamed A. Awad , Azizeh Shadidizaji , Marwa A. Ibrahim , Magdy A. Ghoneim , Mohamad Warda

Extra virgin olive oil (EVOO) has a putative antidiabetic activity mostly attributed to its polyphenol Hydroxytyrosol. In this study, we explored the antidiabetic effects of EVOO and Hydroxytyrosol on an in vivo T2D-simulated rat model as well as in in silico study. Wistar rats were divided into four groups. The first group served as a normal control (NC), while type 2 diabetes (T2D) was induced in the remaining groups using a high-fat diet (HFD) for 12 weeks followed by a single dose of streptozotocin (STZ, 30 mg/kg). One diabetic group remained untreated (DC), while the other two groups received an 8-week treatment with either EVOO (90 g/kg of the diet) (DO) or Hydroxytyrosol (17.3 mg/kg of the diet) (DH). The DC group exhibited hallmark features of established T2D, including elevated fasting blood glucose levels, impaired glucose tolerance, increased HOMA-IR, widespread downregulation of insulin receptor expression, heightened oxidative stress, and impaired β-cell function. In contrast, treatments with EVOO and Hydroxytyrosol elicited an antidiabetic response, characterized by improved glucose tolerance, as indicated by accelerated blood glucose clearance. Systematic analysis revealed the underlying antidiabetic mechanisms: both treatments enhanced insulin receptor expression in the liver and skeletal muscles, increased adiponectin levels, and mitigated oxidative stress. Moreover, while EVOO reduced intramyocellular lipids, Hydroxytyrosol restored adipose tissue insulin sensitivity and enhanced β-cell survival. Molecular docking and dynamics confirm Hydroxytyrosol's high affinity binding to PGC-1α, IRE-1α, and PPAR-γ, particularly IRE-1α, highlighting its potential to modulate diabetic signaling pathways. Collectively, these mechanisms highlight the putative antidiabetic role of EVOO and Hydroxytyrosol. Moreover, the favorable docking scores of Hydroxytyrosol with PGC-1α, IRE-1α, and PPAR-γ support the antidiabetic potential and offer promising avenues for further research and the development of novel antidiabetic therapies.

特级初榨橄榄油（EVOO）具有抗糖尿病活性，这主要归功于其多酚羟基酪醇。在这项研究中，我们探讨了特级初榨橄榄油和羟基酪醇对模拟 T2D 大鼠模型的体内抗糖尿病作用，并进行了硅学研究。Wistar 大鼠分为四组。第一组为正常对照组（NC），其余各组均采用高脂饮食（HFD）诱导 2 型糖尿病（T2D），持续 12 周，然后单剂量注射链脲佐菌素（STZ，30 毫克/千克）。一个糖尿病组仍未接受治疗（DC），而其他两组则接受了为期八周的EVOO（90克/千克食物）（DO）或羟基酪醇（17.3毫克/千克食物）（DH）治疗。DC组表现出已确立的T2D的标志性特征，包括空腹血糖水平升高、糖耐量受损、HOMA-IR升高、胰岛素受体表达广泛下调、氧化应激增加以及β细胞功能受损。与此相反，EVOO 和羟基酪醇可引起抗糖尿病反应，其特点是葡萄糖耐量得到改善，血糖清除率加快。系统分析揭示了其潜在的抗糖尿病机制：这两种疗法都能增强肝脏和骨骼肌中胰岛素受体的表达，提高脂肪连素水平，减轻氧化应激。此外，EVOO 减少了细胞内脂类，而羟基酪醇则恢复了脂肪组织的胰岛素敏感性，并提高了 β 细胞的存活率。分子对接和动力学证实了羟基酪醇与 PGC-1α、IRE-1α 和 PPAR-γ（尤其是 IRE-1α）的高亲和力结合，突显了其调节糖尿病信号通路的潜力。总之，这些机制凸显了EVOO和羟基酪醇可能具有的抗糖尿病作用。此外，羟基酪醇与 PGC-1α、IRE-1α 和 PPAR-γ 的良好对接得分支持了其抗糖尿病的潜力，并为进一步研究和开发新型抗糖尿病疗法提供了前景广阔的途径。

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引用次数: 0