Global Adipose Tissue Remodeling During the First Month of Postnatal Life in Mice

Abstract

During the first month of postnatal life, adipose tissue depots of mice go through a drastic, but transient, remodeling process. Between postnatal days 10 and 20, several white fat depots display a strong and sudden surge in beige adipocyte emergence that reverts until day 30. At the same time, brown fat depots appear to undergo an opposite phenomenon. We comprehensively describe these events, their depot specificity and known environmental and genetic interactions, such as maternal diet, housing temperature and mouse strain. We further discuss potential mechanisms and plausible purposes, including the tempting hypothesis that postnatal transient remodeling creates a lasting adaptive capacity still detectable in adult animals. Finally, we propose postnatal adipose tissue remodeling as a model process to investigate mechanisms of beige adipocyte recruitment advantageous to cold exposure or adrenergic stimulation in its entirely endogenous sequence of events without external manipulation.

Two-step regulation by matrix Gla protein in brown adipose cell differentiation

“…To determine whether MGP plays a role in BAT, we first examined the MGP expression in the interscapular (i)BAT from wild-type and global Mgp knockout mice ( Mgp -KO) mice between p1 to p28. Whereas no MGP was detected in the BAT of the Mgp -KO mice, expression of Mgp gradually increased and peaked around p16 in the wild-type mice ( Figure 1 A), which coincides with the end of the proliferative postnatal growth of BAT on p14 [ 8 ]. We also determined whether Mgp was expressed in the mature brown adipocytes using iBAT from Adipo CreERT ;mTmG mice, where expression of the late adipocyte marker Adiponectin ( Adipoq )-expressing cells abolish tdTomato expression but induce enhanced green fluorescent protein (eGFP) expression.…”

“…BAT differs from WAT during pre- and postnatal development and remodeling in that it is fully developed prior to birth, as determined by tissue mass and Ucp1 expression [ 8 ], which enables the pups to maintain body temperature. Postnatally, the BAT continues to grow, first due to proliferation until P14, and subsequently due to lipid accumulation [ 8 ]. In mouse WAT, a tentative hierarchy has been defined among the ASPCs during development [ 1 , 20 ].…”

“…BAT develops fully prior to birth but continues to grow, mainly due to cell proliferation until postnatal day (p)14, and thereafter by increasing the lipid content [ 8 ]. BAT is abundant in the interscapular and perirenal locations in human infants, whereas adult human BAT is found mainly in the cervical, supraclavicular and paravertebral regions [ 3 , 9 ].…”

Thermogenic adipose tissue aging: Mechanisms and implications

“…Data from murine studies indicate a transient and extensive remodeling of white adipose tissue during the first 3 weeks of life, characterized by the emergence of beige adipocytes, as indicated by increased UCP1 expression in different depots. This peaks at around postnatal day 20 and is reversed at day 30 in C57BL6 mice, and seems to be dependent upon the interaction of genetic and environmental factors and has been thoroughly reviewed elsewhere ( Bruder and Fromme, 2022 ).…”

“…Changes in thermogenic adipose tissue structure and function across the lifespan have been more extensively investigated in animal models ( Bruder and Fromme, 2022 ). Investigation more complex in humans and currently based on anatomical and functional imaging by nuclear magnetic resonance and PET/CT imaging, histological sampling of accessible adipose tissue sites, or postmortem studies ( Kajimura et al, 2015 ; Cohen and Kajimura, 2021 ).…”