小柯机器人

研究发现肥胖加速脱发
2021-06-27 16:04

日本东京医科牙科大学西村荣美研究团队在研究中取得进展。他们揭示肥胖通过以干细胞为中心的收敛机制加速脱发。相关论文于2021年6月23日发表于国际顶尖学术期刊《自然》杂志上。

他们报告肥胖引起的压力,例如由高脂肪饮食 (HFD) 引起的压力,靶向毛囊干细胞 (HFSC)来加速脱发。按时间顺序排列的基因表达分析显示,在年轻小鼠中连续四天喂食 HFD,通过产生过量的活性氧将活化的 HFSCs 导向表皮角化,但不会减少 HFSCs 的数量。使用干细胞命运追踪、表观遗传学和反向遗传学的综合分析表明,进一步喂食 HFD 随后通过自分泌和/或旁分泌 IL-1R 信号诱导 HFSC 内的脂滴和 NF-κB 活化。

这些综合因素集中在 HFSC 中 Sonic Hedgehog (SHH) 信号转导的显著抑制上,从而通过其异常分化进一步消耗富含脂质的 HFSC,并诱导毛囊小型化和最终脱发。相反,SHH 的转基因或药理学激活挽救了 HFD 诱导的脱发。这些数据共同表明,肥胖诱导的干细胞炎症信号强烈抑制器官再生信号以加速微型器官的小型化,并表明日常预防器官功能障碍的重要性。

据介绍,肥胖是一种全球流行病,它使个体易患许多与年龄相关的疾病,但它对器官功能障碍的确切影响在很大程度上是未知的。毛囊——生长毛发的微型上皮器官——随着年龄的增长而缩小,通过耗尽HFSC导致脱发。

附:英文原文

Title: Obesity accelerates hair thinning by stem cell-centric converging mechanisms

Author: Hironobu Morinaga, Yasuaki Mohri, Marina Grachtchouk, Kyosuke Asakawa, Hiroyuki Matsumura, Motohiko Oshima, Naoya Takayama, Tomoki Kato, Yuriko Nishimori, Yuriko Sorimachi, Keiyo Takubo, Takayoshi Suganami, Atsushi Iwama, Yoichiro Iwakura, Andrzej A. Dlugosz, Emi K. Nishimura

Issue&Volume: 2021-06-23

Abstract: Obesity is a worldwide epidemic that predisposes individuals to many age-associated diseases, but its exact effects on organ dysfunction are largely unknown1. Hair follicles—mini-epithelial organs that grow hair—are miniaturized by ageing to cause hair loss through the depletion of hair follicle stem cells (HFSCs)2. Here we report that obesity-induced stress, such as that induced by a high-fat diet (HFD), targets HFSCs to accelerate hair thinning. Chronological gene expression analysis revealed that HFD feeding for four consecutive days in young mice directed activated HFSCs towards epidermal keratinization by generating excess reactive oxygen species, but did not reduce the pool of HFSCs. Integrative analysis using stem cell fate tracing, epigenetics and reverse genetics showed that further feeding with an HFD subsequently induced lipid droplets and NF-κB activation within HFSCs via autocrine and/or paracrine IL-1R signalling. These integrated factors converge on the marked inhibition of Sonic hedgehog (SHH) signal transduction in HFSCs, thereby further depleting lipid-laden HFSCs through their aberrant differentiation and inducing hair follicle miniaturization and eventual hair loss. Conversely, transgenic or pharmacological activation of SHH rescued HFD-induced hair loss. These data collectively demonstrate that stem cell inflammatory signals induced by obesity robustly represses organ regeneration signals to accelerate the miniaturization of mini-organs, and suggests the importance of daily prevention of organ dysfunction.

DOI: 10.1038/s41586-021-03624-x

Source: https://www.nature.com/articles/s41586-021-03624-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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