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

Kasza, I.; Kuehn, J.-P.; Volzke, H.; Hernando, D.; Xu, Y. G.; Siebert, J. W.; Gibson, A. L.; Yen, C.-L. E.; Nelson, D. W.; MacDougald, O. A.; Richardson, N. E.; Lamming, D.; Kern, P. A.; Alexander, C.

doi:10.1101/2020.09.16.300533

bioRxiv · 10.1101/2020.09.16.300533

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

Kasza, I.·Kuehn, J.-P.·Volzke, H.·Hernando, D.·Xu, Y. G.·Siebert, J. W.·Gibson, A. L.·Yen, C.-L. E.·Nelson, D. W.·MacDougald, O. A.·Richardson, N. E.·Lamming, D.·Kern, P. A.·Alexander, C.

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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 function and regulation. For human, we assay a skin-associated fat (SAF) body-wide depot to distinguish it from the subcutaneous fat pads characteristic of 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 {beta}-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 {beta}-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 {beta}-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 defense. The adipose tissue that covers human subjects produces heat directly, providing an alternative to the brown adipose tissues. KEY POINTS SUMMARYO_LISeveral distinct strategies produce and conserve heat to maintain body temperature of mammals, each associated with unique physiologies, with consequence for wellness and disease susceptibility C_LIO_LIHighly regulated properties of skin offset the total requirement for heat production C_LIO_LIWe 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 C_LIO_LIWe 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 C_LIO_LIIn contrast, the body-wide adipose depot associated with human skin produces heat directly, potentially creating an alternative to the centrally regulated brown adipose tissue C_LI

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Kasza, I., Kuehn, J.-P., Volzke, H., Hernando, D., Xu, Y. G., Siebert, J. W., Gibson, A. L., Yen, C.-L. E., Nelson, D. W., MacDougald, O. A., Richardson, N. E., Lamming, D., Kern, P. A., Alexander, C.. 2020-09-18. Contrasting recruitment of skin-associated adipose depots during cold challenge of mouse and human. https://doi.org/10.1101/2020.09.16.300533

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