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氯膦酸盐脂质体助力肥胖研究频登顶刊Cell

更新时间:2024-09-28   点击次数:238次

中文摘要:

米色脂肪在调节全身能量稳态中起关键作用;然而,其激活的详细机制和安全策略仍然难以捉摸。在这项研究中,我们发现针对米色脂肪的局部热疗疗法 (LHT) 促进了其在人类和小鼠中的激活。使用基于水凝胶的光热疗法实现 LHT,激活米色脂肪,预防和治疗小鼠肥胖,无不良反应。HSF1 是效果所必需的,因为 HSF1 缺陷减弱了 LHT 的代谢益处。HSF1 调节 Hnrnpa2b1 (A2b1) 转录,导致关键代谢基因的 mRNA 稳定性增加。重要的是,对人类关联研究的分析以及随后的功能分析表明,HSF1 功能获得性变体 p.P365T 与人类代谢性能的改善以及小鼠和细胞中 A2b1 转录的增加有关。总体而言,我们证明 LHT 通过 HSF1-A2B1 转录轴诱导米色脂肪激活,提供了一种有前途的对抗肥胖的策略。

英文摘要:

Beige fat plays key roles in the regulation of systemic energy homeostasis; however, detailed mechanisms and safe strategy for its activation remain elusive. In this study, we discovered that local hyperthermia therapy (LHT) targeting beige fat promoted its activation in humans and mice. LHT achieved using a hydrogel-based photothermal therapy activated beige fat, preventing and treating obesity in mice without adverse effects. HSF1 is required for the effects since HSF1 deficiency blunted the metabolic benefits of LHT. HSF1 regulates Hnrnpa2b1 (A2b1) transcription, leading to increased mRNA stability of key metabolic genes. Importantly, analysis of human association studies followed by functional analysis revealed that the HSF1 gain-of-function variant p.P365T is associated with improved metabolic performance in humans and increased A2b1 transcription in mice and cells. Overall, we demonstrate that LHT offers a promising strategy against obesity by inducing beige fat activation via HSF1-A2B1 transcriptional axis.

论文信息:

论文题目:Local hyperthermia therapy induces browning of white fat and treats obesity

期刊名称:Cell

时间期卷: Volume 185, Issue 6

在线时间:2022年3月17日

氯膦酸盐脂质体助力肥胖研究频登顶刊Cell:

氯膦酸盐脂质体助力肥胖研究频登顶刊Cell


氯膦酸盐脂质体助力肥胖研究频登顶刊Cell产品引用截图

氯膦酸盐脂质体助力肥胖研究频登顶刊Cell


Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸盐脂质体清除脂肪组织巨噬的给药方案可以参考该Cell文献。

Macrophage depletion in adipose tissues

In prior to macrophage depletion, 8-weeks old mice were injected with PDA/PEG hydrogel (PDA) bilaterally in inguinal fat pads. Two days later, these mice were injected with 110mg/kg of clodronate-loaded liposomes (Liposoma, CP-005-005) every two days for three times. Afterwards, skin areas covering beige fat were illuminated unilaterally on one side of iWAT with an 808-nm near-infrared (NIR) laser for 10 min (LHT) while the other side of iWAT remained unilluminated (Sham). Mice were sacrificed to collect iWAT tissues for further analysis after 24 h.

脂肪组织中巨噬细胞耗竭

在巨噬细胞耗竭之前,在腹股沟脂肪垫中双侧注射 PDA/PEG 水凝胶 (PDA) 的 8 周龄小鼠。两天后,这些小鼠每两天注射 110 mg/kg 负载氯膦酸盐的脂质体 (Liposoma, CP-005-005),持续 3 次。之后,用 808 nm 近红外 (NIR) 激光单侧照射 iWAT 一侧覆盖米色脂肪的皮肤区域 10 分钟 (LHT),而 iWAT 的另一侧保持未照明 (Sham)。24 小时后处死小鼠以收集 iWAT 组织用于进一步分析。

氯膦酸盐脂质体助力肥胖研究频登顶刊Cell


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