Language
English
Publication Date
11-1-2025
Journal
Molecular Metabolism
DOI
10.1016/j.molmet.2025.102252
PMID
40945691
PMCID
PMC12506565
PubMedCentral® Posted Date
9-11-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Objective and methods: Brown adipose tissue (BAT) comprises a heterogeneous population of adipocytes and non-adipocyte cell types. To characterize these cellular subpopulations and their adaptation to cold, we performed single-nucleus mRNA-sequencing (snRNA-seq) on interscapular BAT from mice maintained at room temperature or exposed to acute (24h) or chronic (10 days) cold (6 °C). To investigate the role of the de novo lipogenesis (DNL)-regulating transcription factor carbohydrate response element-binding protein (ChREBP), we analyzed control and brown adipocyte-specific ChREBP knockout mice.
Results: We identified different cell populations, including seven brown adipocyte subtypes with distinct metabolic profiles. One of them highly expressed ChREBP and DNL enzymes. Notably, these lipogenic adipocytes were highly sensitive to acute cold exposure, showing a marked depletion in BAT of control mice that was compensated by other brown adipocyte subtypes maintaining DNL. Chronic cold exposure resulted in an expansion of basal brown adipocytes and adipocytes putatively derived from stromal and endothelial precursors. In ChREBP-deficient mice, lipogenic adipocytes were almost absent under all conditions, identifying the transcription factor as a key determinant of this adipocyte subtype. Detailed expression analyses revealed Ttc25 as a specific marker of lipogenic brown adipocytes and as a downstream target of ChREBP. Furthermore, pathway and cell-cell interaction analyses implicated a Wnt-ChREBP axis in the maintenance of lipogenic adipocytes, with Wnt ligands from stromal and muscle cells providing instructive cues.
Conclusions: Our findings provide a comprehensive atlas of BAT cellular heterogeneity and reveal a critical role for ChREBP in lipogenic adipocyte identity, with implications for BAT plasticity and metabolic function.
Keywords
Animals, Mice, Adipose Tissue, Brown, Thermogenesis, Lipogenesis, Cold Temperature, Adipocytes, Brown, Mice, Knockout, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Male, RNA, Messenger, Mice, Inbred C57BL, Transcription Factors, Adipocytes, Brown adipose tissue, Carbohydrate response element-binding protein, Single nucleus RNA-seq, De novo lipogenesis, Cold exposure, Energy metabolism
Published Open-Access
yes
Recommended Citation
Behrens, Janina; Wang, Tongtong; Kilian, Christoph; et al., "Single-Nucleus mRNA-Sequencing Reveals Dynamics of Lipogenic and Thermogenic Adipocyte Populations in Murine Brown Adipose Tissue in Response to Cold Exposure" (2025). Faculty and Staff Publications. 4074.
https://digitalcommons.library.tmc.edu/baylor_docs/4074