Contrasting recruitment of skin-associated adipose depots during cold challenge of mouse and human

Ildiko Kasza, Jens Peter Kühn, Henry Völzke, Diego Hernando, Yaohui G. Xu, John W. Siebert, Angela L.F. Gibson, C. L.Eric Yen, David W. Nelson, Ormond A. MacDougald, Nicole E. Richardson, Dudley W. Lamming, Philip A. Kern, C. M. Alexander

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Key points: Several distinct strategies produce and conserve heat to maintain the body temperature of mammals, each associated with unique physiologies, with consequences for wellness and disease susceptibility Highly regulated properties of skin offset the total requirement for heat production We hypothesize that the adipose component of skin is primarily responsible for modulating heat flux; here we evaluate the relative regulation of adipose depots in mouse and human, to test their recruitment to heat production and conservation We found that insulating mouse dermal white adipose tissue accumulates in response to environmentally and genetically induced cool stress; this layer is one of two adipose depots closely apposed to mouse skin, where the subcutaneous mammary gland fat pads are actively recruited to heat production In contrast, the body-wide adipose depot associated with human skin produces heat directly, potentially creating an alternative to the centrally regulated brown adipose tissue. Abstract: Mammalian skin impacts metabolic efficiency system-wide, controlling the rate of heat loss and consequent heat production. Here we compare the unique fat depots associated with mouse and human skin, to determine whether they have corresponding functions and regulation. For humans, we assay a skin-associated fat (SAF) body-wide depot to distinguish it from the subcutaneous fat pads characteristic of the abdomen and upper limbs. We show that the thickness of SAF is not related to general adiposity; it is much thicker (1.6-fold) in women than men, and highly subject-specific. We used molecular and cellular assays of β-adrenergic-induced lipolysis and found that dermal white adipose tissue (dWAT) in mice is resistant to lipolysis; in contrast, the body-wide human SAF depot becomes lipolytic, generating heat in response to β-adrenergic stimulation. In mice challenged to make more heat to maintain body temperature (either environmentally or genetically), there is a compensatory increase in thickness of dWAT: a corresponding β-adrenergic stimulation of human skin adipose (in vivo or in explant) depletes adipocyte lipid content. We summarize the regulation of skin-associated adipocytes by age, sex and adiposity, for both species. We conclude that the body-wide dWAT depot of mice shows unique regulation that enables it to be deployed for heat preservation; combined with the actively lipolytic subcutaneous mammary fat pads they enable thermal defence. The adipose tissue that covers human subjects produces heat directly, providing an alternative to the brown adipose tissues.

Original languageEnglish
Pages (from-to)847-868
Number of pages22
JournalJournal of Physiology
Issue number4
StatePublished - Feb 15 2022

Bibliographical note

Funding Information:
We appreciate expert technical assistance from Edgar Ocotl, the University of Wisconsin Translational Research Initiatives in Pathology (TRIP) Laboratory, and the Biobank, supported by the UW Department of Pathology and Laboratory Medicine, UWCCC (P30 CA014520) and the Office of The Director – NIH (S10OD023526). We acknowledge the donation of Sprague–Dawley rat skins from Dr Kumar (Department of Comparative Biosciences, UW).

Funding Information:
This work was supported by RO1GM113142 (C.M.A., I.K.); a pilot award from the University of Wisconsin Skin Disease Research Center (SDRC) NIAMS P30 AR066524 (I.K.); the University of Wisconsin Carbone Comprehensive Cancer Center (UWCCC) for use of its Shared Services (NIH/NCI P30 CA014520), including the Translational Initiatives in Pathology (TrIP) lab and Translational Science Biocore (TSB); R01 DK112282 and UL1 TR001998 (P.K.); R24DK092759, R01DK121759 and R01DK125513 (O.A.M.), UW Institute on Aging, NIA T32 AG000213 (N.E.R.), NIH/National Institute on Aging, AG056771, AG062328, and AG061635 (D.W.L.), the U.S. Department of Veterans Affairs, I01‐BX004031 (D.W.L.) and the facilities and resources from the William S. Middleton Memorial Veterans Hospital. SHIP is part of the Community Medicine Research Net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 01ZZ0701, 03ZIK012), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg‐West Pomerania. Whole‐body MR imaging was supported by a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg‐West Pomerania.

Funding Information:
The University of Greifswald is a member of the ‘Centre of Knowledge Interchange’ programme of Siemens AG. Contrast‐enhanced MRI research is part of the entire whole‐body MRI study and was supported by Bayer Healthcare. The content of the manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work does not represent the views of the Department of Veterans Affairs or the United States Government.

Publisher Copyright:
© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.


  • UCP1
  • brown adipose tissue
  • dWAT
  • dermal white adipose tissue
  • heat production
  • lipolysis
  • obesity
  • scWAT
  • skin-associated fat
  • subcutaneous white adipose tissue
  • thermogenesis
  • β-adrenergic response

ASJC Scopus subject areas

  • Physiology


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