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Dermal white adipose tissue undergoes major morphological changes during the spontaneous and induced murine hair follicle cycling: a reappraisal

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Abstract

In murine skin, dermal white adipose tissue (DWAT) undergoes major changes in thickness in synchrony with the hair cycle (HC); however, the underlying mechanisms remain unclear. We sought to elucidate whether increased DWAT thickness during anagen is mediated by adipocyte hypertrophy or adipogenesis, and whether lipolysis or apoptosis can explain the decreased DWAT thickness during catagen. In addition, we compared HC-associated DWAT changes between spontaneous and depilation-induced hair follicle (HF) cycling to distinguish between spontaneous and HF trauma-induced events. We show that HC-dependent DWAT remodelling is not an artefact caused by fluctuations in HF down-growth, and that dermal adipocyte (DA) proliferation and hypertrophy are HC-dependent, while classical DA apoptosis is absent. However, none of these changes plausibly accounts for HC-dependent oscillations in DWAT thickness. Contrary to previous studies, in vivo BODIPY uptake suggests that increased DWAT thickness during anagen occurs via hypertrophy rather than hyperplasia. From immunohistomorphometry, DWAT thickness likely undergoes thinning during catagen by lipolysis. Hence, we postulate that progressive, lipogenesis-driven DA hypertrophy followed by dynamic switches between lipogenesis and lipolysis underlie DWAT fluctuations in the spontaneous HC, and dismiss apoptosis as a mechanism of DWAT reduction. Moreover, the depilation-induced HC displays increased DWAT thickness, area, and DA number, but decreased DA volume/area compared to the spontaneous HC. Thus, DWAT shows additional, novel HF wounding-related responses during the induced HC. This systematic reappraisal provides important pointers for subsequent functional and mechanistic studies, and introduces the depilation-induced murine HC as a model for dissecting HF–DWAT interactions under conditions of wounding/stress.

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Acknowledgements

We thank the Plikus Lab, namely Prof Maksim Plikus and Raul Ramos (University of California, Irvine), for providing us with the tools and guidance to perform the in vivo BODIPY uptake experiment within their lab and for stimulating discussion and advice.

Funding

Supported in part by the NIHR Manchester Biomedical Research Centre (“Inflammatory Hair Diseases” Programme).

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Authors and Affiliations

Authors

Contributions

AF performed most of the experiments. CN performed BODIPY and TUNEL experiments. AF, CN, and RP analysed the data. MRS contributed mouse skin samples. EH provided experimental advice and helped with data analysis. AF, CN, and RP wrote the manuscript, which was edited by all co-authors. RP conceived and supervised the study.

Corresponding author

Correspondence to Ralf Paus.

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The authors have declared no conflicting interests.

Ethical approval

The spontaneous murine HC experiments were approved by the Committee on Animal Health and Care of the State of Upper Bavaria (Regierung von Oberbayern, Germany).

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Foster, A.R., Nicu, C., Schneider, M.R. et al. Dermal white adipose tissue undergoes major morphological changes during the spontaneous and induced murine hair follicle cycling: a reappraisal. Arch Dermatol Res 310, 453–462 (2018). https://doi.org/10.1007/s00403-018-1831-y

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  • DOI: https://doi.org/10.1007/s00403-018-1831-y

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