Abstract

While beige adipocytes have been found to associate with dense sympathetic neurites in mouse inguinal subcutaneous white fat (iWAT), little is known about when and how this patterning is established. Here, we applied whole-tissue imaging to examine the development of sympathetic innervation in iWAT. We found that parenchymal neurites actively grow between postnatal day 6 (P6) and P28, overlapping with early postnatal beige adipogenesis. Constitutive deletion of Prdm16 in adipocytes led to a significant reduction in early postnatal beige adipocytes and sympathetic density within this window. Using an inducible, adipocyte-specific Prdm16 knockout model, we found that Prdm16 is required for guiding sympathetic growth during early development. Deleting Prdm16 in adult animals, however, did not affect sympathetic structure in iWAT. Together, these findings highlight that beige adipocyte-sympathetic neurite communication is crucial to establish sympathetic structure during the early postnatal period but may be dispensable for its maintenance in mature animals.

Highlights

  • The development of adipose tissue was a critical adaptation for our ancestors

  • Using an inducible, adipocyte-specific Prdm16 knockout mouse model, we found that Prdm16 in beige adipocytes is required for sympathetic axon growth during early development, but not necessary for maintaining sympathetic structure in adulthood. 92 Results 93 Sympathetic innervation of inguinal subcutaneous white fat (iWAT) is established during early postnatal development

  • We analyzed the localization of beige adipocytes using an antibody against uncoupling protein 1 (UCP1), a widely accepted marker for thermogenic adipocytes, and compared their distribution in relation to the sympathetic parenchymal innervation in iWAT using whole-tissue imaging

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Summary

12 Abstract

While beige adipocytes have been found to associate with dense sympathetic neurites in mouse inguinal subcutaneous white fat (iWAT), little is known about when and how this patterning is established. Constitutive deletion of Prdm in adipocytes led to a significant reduction in early postnatal beige adipocytes and sympathetic density within this window. Adipocyte-specific Prdm knockout model, we found that Prdm is required for guiding sympathetic growth during early development. Deleting Prdm in adult animals, did not affect sympathetic structure in iWAT. Together, these findings highlight that beige adipocyte-sympathetic neurite communication is crucial to establish sympathetic structure during the early postnatal period but may be dispensable for its maintenance in mature animals. These findings highlight that beige adipocyte-sympathetic neurite communication is crucial to establish sympathetic structure during the early postnatal period but may be dispensable for its maintenance in mature animals. 26

Introduction
372 Discussion
495 Materials and methods
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