Gene

Cell biology

Neuroscience

Biology

Lipolysis

Endocrinology

Lipogenesis

Brown adipose tissue

Fatty acid

Biochemistry

Endogeny

Internal medicine

Mitochondrion

Transcription factor

Consciousness

Medicine

Involution (esoterism)

Adipose tissue

Carbohydrate-responsive element-binding protein

Cell Reports

<h2>Summary</h2> 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.

Endogenous Fatty Acid Synthesis Drives Brown Adipose Tissue Involution