# Single-nucleus transcriptomes reveal the underlying mechanisms of dynamic whitening in thermogenic adipose tissue in goats

## TL;DR

This study uses single-nucleus RNA sequencing to explore how thermogenic fat in goats turns white, revealing insights into fat cell changes and their implications for obesity and cold adaptation.

## Contribution

The study provides a new cell atlas and identifies gene expression patterns and signaling differences in goat thermogenic adipose tissue during whitening.

## Key findings

- Goat thermogenic adipocytes are more similar to human beige adipocytes than mouse brown adipocytes.
- Beige- and white-like adipocytes share a common origin and can transdifferentiate.
- FGF and CALCR signaling differences suggest lower thermogenic capacity in omental adipose tissue compared to perirenal adipose tissue.

## Abstract

Thermogenic adipose tissue, both beige and brown, experiences whitening as animals are exposed to warmth and age, but the potential mechanisms are not fully understood. In this study, we employed single-nucleus RNA-seq to construct a cell atlas during whitening progression and identified the characteristics of thermogenic adipocytes.

Our histological studies and bulk transcriptome gene expression analysis confirmed that both perirenal and omental adipose tissues (pAT and oAT) exhibited progressive whitening in goats. Compared to the classic brown adipocytes in mice, goat thermogenic adipocytes were more closely related in gene expression patterns to human beige adipocytes, which was also confirmed by adipocyte type- and lineage-specific marker expression analysis. Furthermore, trajectory analysis revealed beige- and white-like adipocytes deriving from a common origin, coexisting and undergoing the transdifferentiation. In addition, differences in gene expression profiles and cell communication patterns (e.g., FGF and CALCR signaling) between oAT and pAT suggested a lower thermogenic capacity of oAT than that of pAT.

We constructed a cell atlas of goat pAT and oAT and descripted the characteristics of thermogenic adipocytes during whitening progression. Altogether, our results make a significant contribution to the molecular and cellular mechanisms behind the whitening of thermogenic adipocytes, and providing new insights into obesity prevention in humans and cold adaptation in animals.

The online version contains supplementary material available at 10.1186/s40104-025-01157-1.