Low-intensity pulsed ultrasound improves metabolic dysregulation in obese mice by suppressing inflammation and extracellular matrix remodeling

IF 3.8 2区 物理与天体物理 Q1 ACOUSTICS
Min He , Hong Zhu , Jingsong Dong , Wenzhen Lin , Boyi Li , Ying Li , Dean Ta
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Abstract

Chronic inflammation in white adipose tissue is crucial in obesity and related metabolic disorders. Low-intensity pulsed ultrasound (LIPUS) is renowned for its anti-inflammatory effects as a non-invasive treatment, yet its precise role in obesity has been uncertain. Our study investigates the therapeutic effect of LIPUS and its underlying mechanism on obesity in mice, thereby offering a novel approach for non-invasive treatment of obesity and associated metabolic disorders for human. Male C57BL/6J mice aged 10 weeks were fed a high-fat diet (HFD) for 8 weeks to establish obesity model, then underwent 8 weeks of LIPUS (frequency: 1.0 MHz, duty cycle: 20 %, Isata: 58–61 mW/cm2, 20 min per day) stimulation of the epididymal white adipose tissue. Fat and lean mass were measured using nuclear magnetic resonance (NMR), while energy homeostasis was evaluated using metabolic cages. Insulin resistance was assessed using glucose tolerance tests (GTT) and insulin tolerance tests (ITT). Regulatory mechanisms were explored using RNA sequencing. Results showed that LIPUS significantly reduced obesity markers in obese mice, including body and adipose tissue weight, and improved insulin resistance, without affecting food intake. RNA sequencing showed 250 up-regulated and 351 down-regulated genes between HFD-LIPUS group and HFD-Sham group, suggesting anti-inflammatory action. Quantitative PCR confirmed reduced pro-inflammatory gene expression and macrophage infiltration in eWAT. Gene set enrichment analysis showed decreased NF-κB signaling and extracellular matrix-receptor interactions in LIPUS-treated mice. Thus, LIPUS effectively mitigates metabolic dysregulation in HFD-induced obesity through inflammation suppression and extracellular matrix remodeling, which provides a potential physical therapy for metabolic syndrome in clinic.
低强度脉冲超声通过抑制炎症和细胞外基质重塑改善肥胖小鼠的代谢失调
白色脂肪组织中的慢性炎症是肥胖和相关代谢紊乱的关键因素。低强度脉冲超声(LIPUS)作为一种非侵入性治疗方法,以其抗炎作用而闻名,但它在肥胖症中的确切作用还不确定。我们的研究调查了 LIPUS 对小鼠肥胖症的治疗效果及其内在机制,从而为人类提供了一种非侵入性治疗肥胖症及相关代谢紊乱的新方法。对年龄为 10 周的雄性 C57BL/6J 小鼠喂食高脂饮食(HFD)8 周以建立肥胖模型,然后对附睾白色脂肪组织进行为期 8 周的 LIPUS(频率:1.0 MHz,占空比:20%,等效功率:58-61 mW/cm2,每天 20 分钟)刺激。使用核磁共振(NMR)测量脂肪和瘦肉质量,使用代谢笼评估能量平衡。胰岛素抵抗通过葡萄糖耐量试验(GTT)和胰岛素耐量试验(ITT)进行评估。利用 RNA 测序探索了调控机制。结果表明,LIPUS能明显降低肥胖小鼠的肥胖指标,包括体重和脂肪组织重量,并改善胰岛素抵抗,而不影响食物摄入量。RNA测序显示,HFD-LIPUS组和HFD-Sham组分别有250个基因上调,351个基因下调,这表明LIPUS具有抗炎作用。定量 PCR 证实,eWAT 中的促炎基因表达和巨噬细胞浸润减少。基因组富集分析表明,LIPUS 治疗小鼠的 NF-κB 信号转导和细胞外基质-受体相互作用减少。因此,LIPUS 通过抑制炎症和细胞外基质重塑,有效缓解了高氟酸膳食诱导的肥胖症代谢失调,为临床治疗代谢综合征提供了一种潜在的物理疗法。
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来源期刊
Ultrasonics
Ultrasonics 医学-核医学
CiteScore
7.60
自引率
19.00%
发文量
186
审稿时长
3.9 months
期刊介绍: Ultrasonics is the only internationally established journal which covers the entire field of ultrasound research and technology and all its many applications. Ultrasonics contains a variety of sections to keep readers fully informed and up-to-date on the whole spectrum of research and development throughout the world. Ultrasonics publishes papers of exceptional quality and of relevance to both academia and industry. Manuscripts in which ultrasonics is a central issue and not simply an incidental tool or minor issue, are welcomed. As well as top quality original research papers and review articles by world renowned experts, Ultrasonics also regularly features short communications, a calendar of forthcoming events and special issues dedicated to topical subjects.
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