A subpopulation of lipogenic brown adipocytes drives thermogenic memory

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Patrick Lundgren - (Autor:in)
  • Prateek V. Sharma - (Autor:in)
  • Lenka Dohnalová - (Autor:in)
  • Kyle Coleman - (Autor:in)
  • Giulia T. Uhr - (Autor:in)
  • Susanna Kircher - (Autor:in)
  • Lev Litichevskiy - (Autor:in)
  • Klaas Bahnsen - , University of Pennsylvania (Autor:in)
  • Hélène C. Descamps - (Autor:in)
  • Christina Demetriadou - (Autor:in)
  • Jacqueline Chan - (Autor:in)
  • Karthikeyani Chellappa - (Autor:in)
  • Timothy O. Cox - (Autor:in)
  • Yael Heyman - (Autor:in)
  • Sarshan R. Pather - (Autor:in)
  • Clarissa Shoffler - (Autor:in)
  • Christopher Petucci - (Autor:in)
  • Ophir Shalem - (Autor:in)
  • Arjun Raj - (Autor:in)
  • Joseph A. Baur - (Autor:in)
  • Nathaniel W. Snyder - (Autor:in)
  • Kathryn E. Wellen - (Autor:in)
  • Maayan Levy - (Autor:in)
  • Patrick Seale - (Autor:in)
  • Mingyao Li - (Autor:in)
  • Christoph A. Thaiss - (Autor:in)

Abstract

Sustained responses to transient environmental stimuli are important for survival. The mechanisms underlying long-term adaptations to temporary shifts in abiotic factors remain incompletely understood. Here, we find that transient cold exposure leads to sustained transcriptional and metabolic adaptations in brown adipose tissue, which improve thermogenic responses to secondary cold encounter. Primary thermogenic challenge triggers the delayed induction of a lipid biosynthesis programme even after cessation of the original stimulus, which protects from subsequent exposures. Single-nucleus RNA sequencing and spatial transcriptomics reveal that this response is driven by a lipogenic subpopulation of brown adipocytes localized along the perimeter of Ucp1hi adipocytes. This lipogenic programme is associated with the production of acylcarnitines, and supplementation of acylcarnitines is sufficient to recapitulate improved secondary cold responses. Overall, our data highlight the importance of heterogenous brown adipocyte populations for ‘thermogenic memory’, which may have therapeutic implications for leveraging short-term thermogenesis to counteract obesity.

Details

OriginalspracheEnglisch
Seiten (von - bis)1691-1705
FachzeitschriftNature metabolism
PublikationsstatusVeröffentlicht - 2 Okt. 2023
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

Scopus 85173094092
PubMed 37783943

Schlagworte

Ziele für nachhaltige Entwicklung