| RRC ID |
88490
|
| 著者 |
Morinaga H, Mohri Y, Grachtchouk M, Asakawa K, Matsumura H, Oshima M, Takayama N, Kato T, Nishimori Y, Sorimachi Y, Takubo K, Suganami T, Iwama A, Iwakura Y, Dlugosz AA, Nishimura EK.
|
| タイトル |
Obesity accelerates hair thinning by stem cell-centric converging mechanisms.
|
| ジャーナル |
Nature
|
| 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.
|
| 巻・号 |
595(7866)
|
| ページ |
266-271
|
| 公開日 |
2021-7-1
|
| DOI |
10.1038/s41586-021-03624-x
|
| PII |
10.1038/s41586-021-03624-x
|
| PMID |
34163066
|
| PMC |
PMC9600322
|
| MeSH |
Alopecia / pathology*
Alopecia / physiopathology*
Animals
Autocrine Communication
Cell Count
Cell Differentiation
Cell Lineage
Cellular Senescence
Diet, High-Fat / adverse effects
Disease Models, Animal
Hair Follicle / pathology*
Hedgehog Proteins / metabolism
Inflammation
Male
Mice
Mice, Inbred C57BL
Obesity / pathology
Obesity / physiopathology*
Oxidative Stress
Paracrine Communication
Receptors, Interleukin-1 / metabolism
Stem Cells / pathology*
|
| IF |
42.779
|
| リソース情報 |
| 実験動物マウス |
RBRC01390 |
