Obesity accelerates hair thinning by stem cell-centric converging mechanisms

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 and Emi K. Nishimura ()
Additional contact information
Hironobu Morinaga: Tokyo Medical and Dental University
Yasuaki Mohri: Tokyo Medical and Dental University
Marina Grachtchouk: University of Michigan Medical School
Kyosuke Asakawa: Tokyo Medical and Dental University
Hiroyuki Matsumura: Tokyo Medical and Dental University
Motohiko Oshima: The University of Tokyo
Naoya Takayama: Chiba University
Tomoki Kato: Tokyo Medical and Dental University
Yuriko Nishimori: Tokyo Medical and Dental University
Yuriko Sorimachi: Research Institute National Center for Global Health and Medicine
Keiyo Takubo: Research Institute National Center for Global Health and Medicine
Takayoshi Suganami: Nagoya University
Atsushi Iwama: The University of Tokyo
Yoichiro Iwakura: Tokyo University of Science
Andrzej A. Dlugosz: University of Michigan Medical School
Emi K. Nishimura: Tokyo Medical and Dental University

Nature, 2021, vol. 595, issue 7866, 266-271

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03624-x Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:595:y:2021:i:7866:d:10.1038_s41586-021-03624-x

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03624-x

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().