# The innate thermogenic capacity of brown adipose tissue develops independently of sympathetic signaling

## TL;DR

Brown fat cells develop their ability to generate heat during fetal development without needing signals from the nervous system.

## Contribution

BAT thermogenic identity forms independently of sympathetic signaling during development.

## Key findings

- BAT thermogenic identity develops during embryogenesis without sympathetic innervation or β-adrenergic signaling.
- Sympathetic nervous system supports BAT activity during stimulation but is not needed for its thermogenic capacity.
- Developmental and cold-induced BAT remodeling are distinct processes.

## Abstract

Brown adipose tissue (BAT) dissipates energy as heat in response to β-adrenergic signaling induced by the sympathetic nervous system (SNS). While this pathway is essential for the cold-induced remodeling and metabolic activity of BAT, its role in developmental programming is unclear. Here, we show that brown adipocytes acquire thermogenic identity during embryogenesis independently of sympathetic innervation and β-adrenergic signaling. Genetic sympathectomy or disrupted β-adrenergic signaling had minimal effects on thermogenic gene expression or tissue morphology during either embryonic or postnatal BAT development in the absence of cold stress. Functional analyses revealed that the SNS is likely required for circulatory support of BAT activity during β-adrenergic stimulation but not for the development of the thermogenic capacity of BAT itself. These findings demonstrate that developmental and cold-responsive BAT remodeling are mechanistically distinct processes. Defining the molecular programs that drive BAT development may reveal new strategies to enhance BAT formation and function without relying on β-adrenergic stimulation.

•Brown adipose tissue (BAT) acquires its thermogenic identity during fetal development in mice.•BAT becomes densely innervated by sympathetic fibers during fetal development.•The thermogenic identity of brown adipocytes develops independently of sympathetic innervation or β-adrenergic signaling.•The SNS supports BAT activity during β-adrenergic stimulation but is dispensable for establishing its thermogenic capacity.

Brown adipose tissue (BAT) acquires its thermogenic identity during fetal development in mice.

BAT becomes densely innervated by sympathetic fibers during fetal development.

The thermogenic identity of brown adipocytes develops independently of sympathetic innervation or β-adrenergic signaling.

The SNS supports BAT activity during β-adrenergic stimulation but is dispensable for establishing its thermogenic capacity.