Obesity accelerates hair thinning by stem cell-centric converging mechanisms.

Autor: Morinaga H; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Mohri Y; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Grachtchouk M; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA., Asakawa K; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Matsumura H; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Oshima M; Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Takayama N; Department of Regenerative Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan., Kato T; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Nishimori Y; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Sorimachi Y; Department of Stem Cell Biology, Research Institute National Center for Global Health and Medicine, Tokyo, Japan., Takubo K; Department of Stem Cell Biology, Research Institute National Center for Global Health and Medicine, Tokyo, Japan., Suganami T; Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan., Iwama A; Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Iwakura Y; Centre for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan., Dlugosz AA; Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA., Nishimura EK; Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. emikn@g.ecc.u-tokyo.ac.jp.; Division of Aging and Regeneration, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. emikn@g.ecc.u-tokyo.ac.jp.; Division of Stem Cell Aging Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. emikn@g.ecc.u-tokyo.ac.jp.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Jul; Vol. 595 (7866), pp. 266-271. Date of Electronic Publication: 2021 Jun 23.
DOI: 10.1038/s41586-021-03624-x
Abstrakt: Obesity is a worldwide epidemic that predisposes individuals to many age-associated diseases, but its exact effects on organ dysfunction are largely unknown 1 . 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.
Databáze: MEDLINE
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