Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution

Research output: Contribution to journalJournal articleResearchpeer-review


  • Christian Schlein
  • Alexander W. Fischer
  • Anna Worthmann
  • Klaus Tödter
  • Michelle Y. Jaeckstein
  • Janina Behrens
  • Matthew D. Lynes
  • Michael A. Kiebish
  • Niven R. Narain
  • Val Bussberg
  • Abena Darkwah
  • Naja Zenius Jespersen
  • Søren Nielsen
  • Michaela Schweizer
  • Ingke Braren
  • Alexander Bartelt
  • Yu Hua Tseng
  • Joerg Heeren
  • Ludger Scheja

Thermoneutral conditions typical for standard human living environments result in brown adipose tissue (BAT) involution, characterized by decreased mitochondrial mass and increased lipid deposition. Low BAT activity is associated with poor metabolic health, and BAT reactivation may confer therapeutic potential. However, the molecular drivers of this BAT adaptive process in response to thermoneutrality remain enigmatic. Using metabolic and lipidomic approaches, we show that endogenous fatty acid synthesis, regulated by carbohydrate-response element-binding protein (ChREBP), is the central regulator of BAT involution. By transcriptional control of lipogenesis-related enzymes, ChREBP determines the abundance and composition of both storage and membrane lipids known to regulate organelle turnover and function. Notably, ChREBP deficiency and pharmacological inhibition of lipogenesis during thermoneutral adaptation preserved mitochondrial mass and thermogenic capacity of BAT independently of mitochondrial biogenesis. In conclusion, we establish lipogenesis as a potential therapeutic target to prevent loss of BAT thermogenic capacity as seen in adult humans.

Original languageEnglish
Article number108624
JournalCell Reports
Issue number2
Number of pages19
Publication statusPublished - 2021

    Research areas

  • brown adipose tissue, cardiolipins, ChREBP, de novo lipogenesis, energy expenditure, fatty acid synthesis, fatty acids, lipidome, mitochondria, mitophagy, non-shivering thermogenesis, phospholipids, thermoneutrality, triacylglycerols, whitening

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