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Assessment of the quality, content, and reliability of YouTube® videos on diabetes mellitus and polycystic ovary syndrome: a systematic review with cross-sectional analysis comparing peer-reviewed videos. YouTube®糖尿病和多囊卵巢综合症视频的质量、内容和可靠性评估:比较同行评审视频的横断面分析系统综述。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-28 Print Date: 2024-07-01 DOI: 10.1530/EC-24-0059
Shams Ali Baig, Kashish Malhotra, Anagh Josh Banerjee, Mukunth Kowsik, Khushi Kumar, Fazna Rahman, Syeda Sabbah Batul, Mohammed Faraaz Saiyed, Vardhan Venkatesh, Pranav Viswanath Iyer, Punith Kempegowda

YouTube® is one of the leading platforms for health information. However, the lack of regulation of content and quality raises concerns about accuracy and reliability. CoMICs (Concise Medical Information Cines) are evidence-based short videos created by medical students and junior doctors and reviewed by experts to ensure clinical accuracy. We performed a systematic review to understand the impact of videos on knowledge and awareness about diabetes and PCOS. We then evaluated the quality of YouTube® videos about diabetes and PCOS using various validated quality assessment tools and compared these with CoMICs videos on the same topics. Quality assessment tools like DISCERN, JAMA benchmark criteria, and global quality scale (GQS) score were employed. Some of the authors of this study also co-authored the creation of some of the CoMICs evaluated. Our study revealed that while videos effectively improve understanding of diabetes and PCOS, there are notable differences in quality and reliability of the videos on YouTube®. For diabetes, CoMICs videos had higher DISCERN scores (CoMICs vs YouTube®: 2.4 vs 1.6), superior reliability (P < 0.01), and treatment quality (P < 0.01) and met JAMA criteria for authorship (100% vs 30.6%) and currency (100% vs 53.1%). For PCOS, CoMICs had higher DISCERN scores (2.9 vs 1.9), reliability (P < 0.01), and treatment quality (P < 0.01); met JAMA criteria for authorship (100% vs 34.0%) and currency (100% vs 54.0%); and had higher GQS scores (4.0 vs 3.0). In conclusion, CoMICs outperformed other similar sources on YouTube® in providing reliable evidence-based medical information which may be used for patient education.

YouTube® 是健康信息的主要平台之一。然而,由于缺乏对内容和质量的监管,人们对其准确性和可靠性产生了担忧。CoMIC(简明医学信息视频)是由医科学生和初级医生制作的基于证据的短视频,并由专家进行审核,以确保临床准确性。我们进行了一项系统性回顾,以了解视频对糖尿病和多囊卵巢综合症知识和认知的影响。然后,我们使用各种经过验证的质量评估工具对 YouTube® 上有关糖尿病和多囊卵巢综合症的视频进行了质量评估,并将其与 CoMICs 上相同主题的视频进行了比较。我们使用了 DISCERN、JAMA 基准标准和全球质量评分 (GQS) 等质量评估工具。本研究的一些作者还与他人共同创作了一些被评估的 CoMICs。我们的研究表明,虽然视频能有效增进人们对糖尿病和多囊卵巢综合症的了解,但 YouTube® 上的视频在质量和可靠性方面存在明显差异。在糖尿病方面,CoMICs 视频的 DISCERN 分数更高(CoMICs vs YouTube®:2.4 vs 1.6),可靠性更高(p
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引用次数: 0
Cold exposure increases circulating fibroblast growth factor 21 in the evening in males and females. 傍晚时分,男性和女性体内的循环成纤维细胞生长因子 21 会因寒冷而增加。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-18 Print Date: 2024-07-01 DOI: 10.1530/EC-24-0074
Carlijn A Hoekx, Borja Martinez-Tellez, Maaike E Straat, Magdalena M A Verkleij, Mirjam Kemmeren, Sander Kooijman, Martin Uhrbom, Saskia C A de Jager, Patrick C N Rensen, Mariëtte R Boon

Objectives: Cold exposure is linked to cardiometabolic benefits. Cold activates brown adipose tissue (BAT), increases energy expenditure, and induces secretion of the hormones fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). The cold-induced increase in energy expenditure exhibits a diurnal rhythm in men. Therefore, we aimed to investigate the effect of cold exposure on serum FGF21 and GDF15 levels in humans and whether cold-induced changes in FGF21 and GDF15 levels differ between morning and evening in males and females.

Method: In this randomized cross-over study, serum FGF21 and GDF15 levels were measured in healthy lean males (n = 12) and females (n = 12) before, during, and after 90 min of stable cold exposure in the morning (07:45 h) and evening (19:45 h) with a 1-day washout period in between.

Results: Cold exposure increased FGF21 levels in the evening compared to the morning both in males (+61% vs -13%; P < 0.001) and in females (+58% vs +8%; P < 0.001). In contrast, cold exposure did not significantly modify serum GDF15 levels, and no diurnal variation was found. Changes in FGF21 and GDF15 levels did not correlate with changes in cold-induced energy expenditure in the morning and evening.

Conclusion: Cold exposure increased serum FGF21 levels in the evening, but not in the morning, in both males and females. GDF15 levels were not affected by cold exposure. Thus, this study suggests that the timing of cold exposure may influence cold-induced changes in FGF21 levels but not GDF15 levels and seems to be independent of changes in energy expenditure.

目的:寒冷与心脏代谢的益处有关。寒冷可激活棕色脂肪组织(BAT),增加能量消耗,并诱导成纤维细胞生长因子 21(FGF21)和生长分化因子 15(GDF15)等激素的分泌。寒冷引起的能量消耗增加在男性中表现出昼夜节律。因此,我们旨在研究寒冷暴露对人体血清 FGF21 和 GDF15 水平的影响,以及寒冷诱导的 FGF21 和 GDF15 水平变化在男性和女性的早晚是否有所不同:在这项随机交叉研究中,分别在早晨(7:45am)和傍晚(7:45pm)进行90分钟稳定的冷暴露之前、期间和之后,测量健康瘦男性(n=12)和女性(n=12)的血清FGF21和GDF15水平,中间有一天的冲洗期:结果:与早晨相比,男性在傍晚暴露于寒冷会增加 FGF21 水平(+61% 对 -13%;PC 结论:暴露于寒冷会增加血清中的 FGF21 水平:寒冷暴露会增加男性和女性晚上的血清 FGF21 水平,而不是早上的水平。GDF15 的水平不受寒冷影响。因此,这项研究表明,寒冷暴露的时间可能会影响寒冷诱导的 FGF21 水平变化,但不会影响 GDF15 水平,而且似乎与能量消耗的变化无关。
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引用次数: 0
Diagnostic accuracy of Afirma gene expression classifier, Afirma gene sequencing classifier, ThyroSeq v2 and ThyroSeq v3 for indeterminate (Bethesda III and IV) thyroid nodules: a meta-analysis. Afirma 基因表达分类器、Afirma 基因测序分类器、ThyroSeq v2 和 ThyroSeq v3 对不确定甲状腺结节(Bethesda III 和 IV)的诊断准确性:一项荟萃分析。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-13 Print Date: 2024-07-01 DOI: 10.1530/EC-24-0170
Irfan Vardarli, Susanne Tan, Rainer Görges, Bernhard K Krämer, Ken Herrmann, Christoph Brochhausen

Objective: The management of thyroid nodules with indeterminate cytology (ITN) is still a challenge. To evaluate the performance of commercial molecular tests for ITN, we performed this comprehensive meta-analysis.

Methods: We performed an electronic search using PubMed/Medline, Embase, and the Cochrane Library. Studies assessing the diagnostic accuracy of Afirma gene expression classifier (GEC), Afirma gene sequencing classifier (GSC), ThyroSeq v2 (TSv2), or ThyroSeq v3 (TSv3) in patients with ITN (only Bethesda category III or IV) were selected; Statistical analyses were performed by using Stata.

Results: Seventy-one samples (GEC, n = 38; GSC, n = 16; TSv2, n = 9; TSv3, n = 8) in 53 studies, involving 6490 fine needle aspirations (FNAs) with ITN cytology with molecular diagnostics (GEC, GSC, TSv2, or TSv3), were included in the study. The meta-analysis showed the following pooled estimates: sensitivity 0.95 (95% CI: 0.94-0.97), specificity 0.35 (0.28-0.43), positive likelihood ratio (LR+) 1.5 (1.3-1.6), and negative likelihood ratio (LR-) 0.13 (0.09-0.19), with the best performance for TSv3 (area under the ROC curve 0.95 (0.93-0.96), followed by TSv2 (0.90 (0.87-0.92)), GSC (0.86 (0.82-0.88)), and GEC (0.82 (0.78-0.85)); the best rule-out property was observed for GSC (LR-, 0.07 (0.02-0.19)), followed by TSv3 (0.11 (0.05-0.24)) and GEC (0.16 (0.10-0.28), and the best rule-in was observed for TSv2 (LR+, 2,9 (1.4-4.6)), followed by GSC (1.9 (1.6-2.4)). A meta-regression analysis revealed that study design, Bethesda category, and type of molecular test were independent factors.

Conclusion: We showed that in patients with ITN, TSv3 has the best molecular diagnostic performance, followed by TSv2, GSC, and GEC. As regards rule-out malignancy, GSC, and rule-in, TSV2 is superior to other tests.

目的:对细胞学(ITN)不确定的甲状腺结节的处理仍是一项挑战。为了评估商用分子检验在 ITN 方面的性能,我们进行了这项综合荟萃分析:我们使用 PubMed/Medline、Embase 和 Cochrane 图书馆进行了电子检索。筛选出评估 Afirma 基因表达分类器 (GEC)、Afirma 基因测序分类器 (GSC)、ThyroSeq v2 (TSv2) 或 ThyroSeq v3 (TSv3) 对 ITN 患者(仅 Bethesda III 或 IV 类)诊断准确性的研究;使用 Stata 进行统计分析:53项研究中的71个样本(GEC,n=38;GSC,n=16;TSv2,n=9;TSv3,n=8)被纳入研究,涉及6490例ITN细胞学分子诊断(GEC、GSC、TSv2或TSv3)的细针穿刺(FNA)。Meta 分析显示了以下汇总估计值:灵敏度 0.95(95% CI,0.94-0.97),特异性 0.35(0.28-0.43),阳性似然比 (LR+) 1.5(1.3-1.6),阴性似然比 (LR-) 0.13(0.09-0.19),其中 TSv3 的表现最佳(ROC 曲线下面积 0.95(0.93-0.96),其次是 TSv2。96),其次是 TSv2(0.90(0.87-0.92))、GSC(0.86(0.82-0.88))和 GEC(0.82(0.78-0.85));排除性能最好的是 GSC(LR-,0.07(0.02-0.19)),其次是 TSv3(0.11(0.05-0.24))和 GEC(0.16(0.10-0.28));TSv2 的规则入属性最好(LR+,2.9(1.4-4.6)),其次是 GSC(1.9(1.6-2.4))。元回归分析显示,研究设计、贝塞斯达类别和分子检测类型是独立因素:我们发现,在 ITN 患者中,TSv3 的分子诊断效果最好,其次是 TSv2、GSC 和 GEC。在排除恶性肿瘤方面,GSC和TSV2优于其他检验。
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引用次数: 0
SLC7A11 promotes EMT and metastasis in invasive pituitary neuroendocrine tumors by activating the PI3K/AKT signaling pathway. SLC7A11通过激活PI3K/AKT信号通路促进侵袭性垂体神经内分泌肿瘤的EMT和转移。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-03 Print Date: 2024-07-01 DOI: 10.1530/EC-24-0097
Shikai Gui, Wanli Yu, Jiabao Xie, Lunshan Peng, Yuanyuan Xiong, Zhen Song, Haitao Luo, Juexian Xiao, Shengtao Yuan, Zujue Cheng

Invasive pituitary neuroendocrine tumors (PitNETs) are the most prevalent types of intracranial and neuroendocrine tumors. Their aggressive growth and difficulty in complete resection result in a high recurrence rate. Cystine transporter solute carrier family 7 member 11 (SLC7A11) is overexpressed in various cancers, which contributes to tumor growth, progression, and metastasis by promoting cystine uptake and glutathione biosynthesis. We identified SLC7A11 as an invasive biomarker based on three Gene Expression Omnibus cohorts. This study aimed to investigate the role of SLC7A11 in invasive PitNETs. Cell proliferation was assessed using CCK-8 and colony formation assays, while cell apoptosis was estimated with flow cytometry. Wound healing assays and transwell assays were utilized to evaluate migration and invasion ability. Our findings demonstrated that SLC7A11 was markedly upregulated in invasive PitNETs, and was associated with the invasiveness of PitNETs. Knockdown of SLC7A11 could largely suppress tumor cell proliferation, migration, and invasion, while inducing apoptosis. Furthermore, SLC7A11 depletion was implicated in regulating epithelial-mesenchymal transition and inactivating the PI3K/AKT signaling pathway. These insights suggest SLC7A11 as a potential therapeutic target for invasive PitNETs.

侵袭性垂体神经内分泌肿瘤(PitNETs)是颅内和神经内分泌肿瘤中最常见的类型。由于其生长具有侵袭性,难以完全切除,因此复发率很高。胱氨酸转运体溶质运载家族 7 成员 11(SLC7A11)在多种癌症中过度表达,通过促进胱氨酸摄取和谷胱甘肽的生物合成,促使肿瘤生长、恶化和转移。我们基于三个 GEO 队列发现 SLC7A11 是一种侵袭性生物标记物。本研究旨在探讨SLC7A11在侵袭性PitNET中的作用。细胞增殖采用CCK-8和集落形成试验进行评估,细胞凋亡采用流式细胞术进行估计。伤口愈合试验和透孔试验用于评估迁移和侵袭能力。我们的研究结果表明,SLC7A11在侵袭性PitNET中明显上调,并且与PitNET的侵袭性有关。敲除SLC7A11能在很大程度上抑制肿瘤细胞的增殖、迁移和侵袭,同时诱导细胞凋亡。此外,SLC7A11的耗竭还与调节EMT和使PI3K/AKT信号通路失活有关。这些发现表明,SLC7A11是侵袭性PitNET的潜在治疗靶点。
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引用次数: 0
Society for Endocrinology guidelines for the diagnosis and management of post-bariatric hypoglycaemia. 内分泌学会(SfE)关于减肥后低血糖诊断和管理的指南。
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-01 Epub Date: 2024-04-01 DOI: 10.1530/EC-23-0285
Jonathan Hazlehurst, Bernard Khoo, Carolina Brito Lobato, Ibiyemi Ilesanmi, Sally Abbott, Tin Chan, Sanesh Pillai, Kate Maslin, Sanjay Purkayastha, Barbara McGowan, Rob Andrews, Tricia M-M Tan

Post bariatric hypoglycaemia (PBH) is typically a post-prandial hypoglycaemia occurring about 2-4 hours after eating in people who have undergone bariatric surgery. PBH develops relatively late after surgery and often after discharge from post-surgical follow-up by bariatric teams, leading to variability in diagnosis and management in non-specialist centres.

Aim: to improve and standardise clinical practice in the diagnosis and management of PBH.

Objectives: (1) to undertake an up-to-date review of the current literature; (2) to formulate practical and evidence-based guidance with regards on the diagnosis and treatment of PBH; (3) to recommend future avenues for research in this condition.

Method: A scoping review was undertaken after an extensive literature search. A consensus on the guidance and confidence in the recommendations was reached by the steering group authors prior to review by key stakeholders.

Outcome: We make pragmatic recommendations for the practical diagnosis and management of PBH including criteria for diagnosis and recognition, as well as recommendations for research areas that should be explored.

减肥术后低血糖症(PBH)通常是指接受减肥手术的患者在进食后约 2-4 小时出现的餐后低血糖症。目标:(1)对当前文献进行最新综述;(2)就 PBH 的诊断和治疗制定实用的循证指南;(3)就该病症的未来研究方向提出建议:方法:在进行了广泛的文献检索后,进行了范围界定审查。方法:在进行了广泛的文献检索后,进行了范围界定审查,指导小组的作者们就指导意见和对建议的信心达成了共识,然后由主要利益相关者进行审查:我们为 PBH 的实际诊断和管理提出了务实的建议,包括诊断和识别标准,以及应探索的研究领域的建议。
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引用次数: 0
Optimal body mass index for protecting middle-aged and elderly patients with fatty liver from future fractures. 保护中老年脂肪肝患者避免未来骨折的最佳体重指数。
IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-01 DOI: 10.1530/EC-24-0089
Hsiao-Yun Yeh, Hung-Ta Hondar Wu, Hsiao-Chin Shen, Tzu-Hao Li, Ying-Ying Yang, Kuei-Chuan Lee, Yi-Hsuan Lin, Chia-Chang Huang, Ming-Chih Hou

Objective: Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes.

Methods: This retrospective cohort study from 2011 to 2019 enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (DXA, for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes, and the effect of different ranges of BMI (18.5-24, 24-27, and ≥27 kg/m2 in women; 18.5-24, 24-27, 27-30 and ≥30 kg/m2 in men) on the risk of future fractures in FL patients.

Results: The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors for osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24-27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5-24 kg/m2.

Conclusion: The protective effect of a higher BMI against future fractures in middle-aged and elderly women and men with FL is not uniform and decreases beyond certain BMI ranges.

研究目的以往的研究表明,在评估脂肪肝(FL)与骨质疏松症之间的关系时,应考虑体重指数(BMI)。本研究旨在调查脂肪肝患者未来的骨折事件,重点关注体重指数对男女患者的影响:这项从 2011 年到 2019 年的回顾性队列研究共招募了 941 人,包括 441 名女性和 500 名男性,年龄均在 50 岁或以上,他们都接受了肝脏成像(超声波、计算机断层扫描或磁共振成像)和双能 X 射线吸收测量(DXA,用于测量骨矿密度)。该研究探讨了男女骨质疏松症的预测因素,以及不同范围的体重指数(女性为 18.5-24、24-27 和≥27 kg/m2;男性为 18.5-24、24-27、27-30 和≥30 kg/m2)对 FL 患者未来骨折风险的影响:女性平均随访 5.3 年,男性平均随访 4.2 年。多变量分析发现,年龄和体重指数是男女骨质疏松症的独立风险因素。体重指数每增加一个单位,骨质疏松症的风险就会降低≥10%。在患有 FL 的女性和男性中,与没有 FL 且 BMI 为 18.5-24 kg/m2 的人相比,BMI 为 24-27 kg/m2 的人可防止未来发生骨折:结论:较高的体重指数对患有 FL 的中老年女性和男性未来骨折的保护作用并不一致,超过一定的体重指数范围后,保护作用就会减弱。
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引用次数: 0
High-intensity interval training combining rowing and cycling improves but does not restore beta-cell function in type 2 diabetes. 结合划船和骑自行车的高强度间歇训练能改善但不能恢复 2 型糖尿病患者的β细胞功能。
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-12 Print Date: 2024-05-01 DOI: 10.1530/EC-23-0558
Maria Houborg Petersen, Jacob Volmer Stidsen, Martin Eisemann de Almeida, Emil Kleis Wentorf, Kurt Jensen, Niels Ørtenblad, Kurt Højlund

Aim: We investigated whether a high-intensity interval training (HIIT) protocol could restore beta-cell function in type 2 diabetes compared with sedentary obese and lean individuals.

Materials and methods: In patients with type 2 diabetes, and age-matched, glucose-tolerant obese and lean controls, we examined the effect of 8 weeks of supervised HIIT combining rowing and cycling on the acute (first-phase) and second-phase insulin responses, beta-cell function adjusted for insulin sensitivity (disposition index), and serum free fatty acid (FFA) levels using the Botnia clamp (1-h IVGTT followed by 3-h hyperinsulinemic-euglycemic clamp).

Results: At baseline, patients with type 2 diabetes had reduced insulin sensitivity (~40%), acute insulin secretion (~13-fold), and disposition index (>35-fold), whereas insulin-suppressed serum FFA was higher (⁓2.5-fold) compared with controls (all P < 0.05). The HIIT protocol increased insulin sensitivity in all groups (all P < 0.01). In patients with type 2 diabetes, this was accompanied by a large (>200%) but variable improvement in the disposition index (P < 0.05). Whereas insulin sensitivity improved to the degree seen in controls at baseline, the disposition index remained markedly lower in patients with type 2 diabetes after HIIT (all P < 0.001). In controls, HIIT increased the disposition index by ~20-30% (all P < 0.05). In all groups, the second-phase insulin responses and insulin-suppressed FFA levels were reduced in response to HIIT (all P < 0.05). No group differences were seen in these HIIT-induced responses.

Conclusion: HIIT combining rowing and cycling induced a large but variable increase in beta-cell function adjusted for insulin sensitivity in type 2 diabetes, but the disposition index remained severely impaired compared to controls, suggesting that this defect is less reversible in response to exercise training than insulin resistance.

Trial registration: ClinicalTrials.gov (NCT03500016).

目的:与久坐不动的肥胖者和瘦人相比,我们研究了高强度间歇训练(HIIT)方案能否恢复2型糖尿病患者的β细胞功能:在2型糖尿病患者以及年龄匹配、葡萄糖耐受性好的肥胖和瘦弱对照组中,我们使用Botnia钳夹法(1小时IVGTT后3小时高胰岛素血糖钳夹)研究了8周有监督的划船和骑自行车相结合的HIIT对急性(第一阶段)和第二阶段胰岛素反应、根据胰岛素敏感性(处置指数)调整的β细胞功能以及血清游离脂肪酸(FFA)水平的影响:结果:基线时,2 型糖尿病患者的胰岛素敏感性降低(约 40%),胰岛素急性分泌降低(约 13 倍),处置指数降低(>35 倍),而与对照组相比,胰岛素抑制的血清游离脂肪酸更高(⁓2.5 倍)(均为 P200%),但处置指数有不同程度的改善(PC结论:结合划船和骑自行车的 HIIT 可诱导 2 型糖尿病患者胰岛素敏感性调整后的β细胞功能大幅提高,但提高幅度不一,但与对照组相比,处置指数仍严重受损,这表明与胰岛素抵抗相比,这种缺陷对运动训练的可逆性较差。
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引用次数: 0
Kaempferol alleviates adipose tissue inflammation and insulin resistance in db/db mice by inhibiting the STING/NLRP3 signaling pathway. 堪非醇通过抑制 STING/NLRP3 信号通路,减轻 db/db 小鼠脂肪组织炎症和胰岛素抵抗。
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-08 Print Date: 2024-05-01 DOI: 10.1530/EC-23-0379
Huiyuan Zhai, Dongxu Wang, Yong Wang, Hongwei Gu, Juan Jv, Liangliang Yuan, Chao Wang, Leiyao Chen

Chronic inflammation induced by obesity plays a crucial role in the pathogenesis of insulin resistance. The infiltration of macrophages into adipose tissues contributes to adipose tissue inflammation and insulin resistance. Kaempferol, a flavonoid present in various vegetables and fruits, has been shown to possess remarkable anti-inflammatory properties. In this study, we used leptin receptor-deficient obese mice (db/db) as an insulin-resistant model and investigated the effects of kaempferol treatment on obesity-induced insulin resistance. Our findings revealed that the administration of kaempferol (50 mg/kg/day, for 6 weeks) significantly reduced body weight, fat mass, and adipocyte size. Moreover, it effectively ameliorated abnormal glucose tolerance and insulin resistance in db/db mice. In the adipose tissue of obese mice treated with kaempferol, we observed a reduction in macrophage infiltration and a downregulation of mRNA expression of M1 marker genes TNF-α and IL-1β, accompanied by an upregulation of Arg1 and IL-10 mRNA expression. Additionally, kaempferol treatment significantly inhibited the STING/NLRP3 signaling pathway in adipose tissue. In vitro experiments, we further discovered that kaempferol treatment suppressed LPS-induced inflammation through the activation of NLRP3/caspase 1 signaling in RAW 264.7 macrophages. Our results suggest that kaempferol may effectively alleviate inflammation and insulin resistance in the adipose tissue of db/db mice by modulating the STING/NLRP3 signaling pathway.

肥胖引发的慢性炎症在胰岛素抵抗的发病机制中起着至关重要的作用。巨噬细胞渗入脂肪组织会导致脂肪组织炎症和胰岛素抵抗。山奈酚是一种存在于多种蔬菜和水果中的类黄酮,已被证明具有显著的抗炎特性。在这项研究中,我们使用瘦素受体缺陷肥胖小鼠(db/db)作为胰岛素抵抗模型,研究了山奈酚治疗对肥胖诱导的胰岛素抵抗的影响。我们的研究结果表明,服用山奈酚(50 毫克/千克/天,连续 6 周)可显著降低体重、脂肪量和脂肪细胞体积。此外,它还能有效改善 db/db 小鼠的糖耐量异常和胰岛素抵抗。在接受山奈酚治疗的肥胖小鼠的脂肪组织中,我们观察到巨噬细胞浸润减少,M1 标记基因 TNF-α 和 IL-1β mRNA 表达下调,同时 Arg1 和 IL-10 mRNA 表达上调。此外,山奈酚还能显著抑制脂肪组织中的 STING/NLRP3 信号通路。在体外实验中,我们进一步发现山奈酚处理可通过激活 RAW 264.7 巨噬细胞中的 NLRP3/caspase-1 信号传导来抑制 LPS 诱导的炎症。我们的研究结果表明,山奈酚可通过调节 STING/NLRP3 信号通路,有效缓解 db/db 小鼠脂肪组织的炎症和胰岛素抵抗。
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引用次数: 0
The distinct hepatic metabolic profile and relation with impaired liver function in congenital isolated growth hormone-deficient rats. 先天性离体生长激素缺乏大鼠不同的肝脏代谢特征及其与肝功能受损的关系。
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-04 Print Date: 2024-05-01 DOI: 10.1530/EC-23-0462
Xiaonan Guo, Wenjing Hu, Xiaorui Lyu, Hanyuan Xu, Huijuan Zhu, Hui Pan, Linjie Wang, Hongbo Yang, Fengying Gong

Objective: Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions.

Methods: Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis.

Results: The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered.

Conclusion: Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.

目的:生长激素水平不足的生长激素缺乏症(GHD)患者通常与非酒精性脂肪肝(NAFLD)相关。然而,GHD影响肝功能的潜在机制仍不清楚。因此,我们旨在对Lewis侏儒大鼠(一种经典的离体生长激素缺乏大鼠模型)进行肝脏代谢组学研究,以评估肝脏代谢轮廓的特征,并探讨它们与肝功能的关系:我们的研究分析了37周的Lewis矮小同基因(dw/dw)大鼠(雌性5只,雄性5只)和37周的Lewis矮小异基因(dw/+)大鼠(雌性5只,雄性5只)。研究人员测量了大鼠的体长和体重、肝脏重量、血清谷丙转氨酶和谷草转氨酶水平。对 dw/+ 和 dw/dw 大鼠进行了非靶向肝脏代谢组学研究:结果:与 dw/+ 大鼠相比,dw/dw 大鼠的体重和体长、肝脏重量以及血清 IGF-1 水平均显著下降。Dw/dw大鼠表现出更明显的肝脏脂肪变性,同时血清ALT和AST水平升高。肝脏代谢组学研究显示,阳性和阴性模式下分别鉴定出 88 和 51 种代谢物。其中七种代谢物(LPC 16:2、LPC 18:3、LPC 22:6、FAHFA18:1、棕榈酰酸、脱氢胆酸和 7-Ketolithocholic acid)发生了显著变化。这七种差异代谢物与异常表型明显相关。KEGG通路分析表明,精氨酸和脯氨酸代谢及胆汁分泌通路主要聚集在一起:结论:孤立性生长激素缺乏症(IGHD)的 Lewis dw/dw 大鼠表现出肝脏脂肪变性和肝功能异常,这可能与独特的肝脏代谢特征有关。
{"title":"The distinct hepatic metabolic profile and relation with impaired liver function in congenital isolated growth hormone-deficient rats.","authors":"Xiaonan Guo, Wenjing Hu, Xiaorui Lyu, Hanyuan Xu, Huijuan Zhu, Hui Pan, Linjie Wang, Hongbo Yang, Fengying Gong","doi":"10.1530/EC-23-0462","DOIUrl":"10.1530/EC-23-0462","url":null,"abstract":"<p><strong>Objective: </strong>Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions.</p><p><strong>Methods: </strong>Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis.</p><p><strong>Results: </strong>The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered.</p><p><strong>Conclusion: </strong>Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11046350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From classical dualistic antagonism to hormone synergy: potential of overlapping action of glucagon, insulin and GLP-1 for the treatment of diabesity 从传统的二元拮抗到激素协同作用:胰高血糖素、胰岛素和 GLP-1 重叠作用治疗肥胖症的潜力
IF 2.9 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-01 DOI: 10.1530/ec-23-0529
Svjatoslavs Kistkins, Othmar Moser, Vitālijs Ankudovičs, Dmitrijs Bliznuks, Timurs Mihailovs, Sergejs Lobanovs, Harald Sourij, Andreas F. H. Pfeiffer, Valdis Pirags

The increasing prevalence of "diabesity," a combination of type 2 diabetes and obesity, poses a significant global health challenge. Unhealthy lifestyle factors, including poor diet, sedentary behavior, and high stress levels, combined with genetic and epigenetic factors, contribute to the diabesity epidemic. Diabesity leads to various significant complications such as cardiovascular diseases, stroke, and certain cancers. Incretin-based therapies, such as GLP-1 receptor agonists and dual hormone therapies, have shown promising results in improving glycemic control and inducing weight loss. However, these therapies also come with certain disadvantages, including withdrawal effects. This review aims to provide insights into the cross-interactions of insulin, glucagon, and GLP-1, revealing the complex hormonal dynamics during fasting and postprandial states, impacting glucose homeostasis, energy expenditure, and other metabolic functions. Understanding these hormonal interactions may offer novel hypotheses in the development of "anti-diabesity" treatment strategies. The article also explores the question of the antagonism of insulin and glucagon, providing insights into the potential synergy and hormonal overlaps between these hormones.

肥胖症 "是 2 型糖尿病和肥胖症的综合征,其发病率的不断上升对全球健康构成了重大挑战。不健康的生活方式,包括不良饮食习惯、久坐不动和高度紧张,再加上遗传和表观遗传因素,导致了肥胖症的流行。肥胖症会导致各种严重并发症,如心血管疾病、中风和某些癌症。以内分泌为基础的疗法,如 GLP-1 受体激动剂和双激素疗法,在改善血糖控制和减轻体重方面显示出良好的效果。然而,这些疗法也有一些缺点,包括戒断效应。本综述旨在深入探讨胰岛素、胰高血糖素和 GLP-1 的交叉相互作用,揭示空腹和餐后状态下复杂的激素动态,从而影响葡萄糖稳态、能量消耗和其他代谢功能。了解这些激素的相互作用可为开发 "抗肥胖 "治疗策略提供新的假设。文章还探讨了胰岛素和胰高血糖素的拮抗作用问题,为这些激素之间潜在的协同作用和激素重叠提供了见解。
{"title":"From classical dualistic antagonism to hormone synergy: potential of overlapping action of glucagon, insulin and GLP-1 for the treatment of diabesity","authors":"Svjatoslavs Kistkins, Othmar Moser, Vitālijs Ankudovičs, Dmitrijs Bliznuks, Timurs Mihailovs, Sergejs Lobanovs, Harald Sourij, Andreas F. H. Pfeiffer, Valdis Pirags","doi":"10.1530/ec-23-0529","DOIUrl":"https://doi.org/10.1530/ec-23-0529","url":null,"abstract":"<p>The increasing prevalence of \"diabesity,\" a combination of type 2 diabetes and obesity, poses a significant global health challenge. Unhealthy lifestyle factors, including poor diet, sedentary behavior, and high stress levels, combined with genetic and epigenetic factors, contribute to the diabesity epidemic. Diabesity leads to various significant complications such as cardiovascular diseases, stroke, and certain cancers. Incretin-based therapies, such as GLP-1 receptor agonists and dual hormone therapies, have shown promising results in improving glycemic control and inducing weight loss. However, these therapies also come with certain disadvantages, including withdrawal effects. This review aims to provide insights into the cross-interactions of insulin, glucagon, and GLP-1, revealing the complex hormonal dynamics during fasting and postprandial states, impacting glucose homeostasis, energy expenditure, and other metabolic functions. Understanding these hormonal interactions may offer novel hypotheses in the development of \"anti-diabesity\" treatment strategies. The article also explores the question of the antagonism of insulin and glucagon, providing insights into the potential synergy and hormonal overlaps between these hormones.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":"1 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140596879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Endocrine Connections
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