White adipose remodeling during browning in mice involves YBX1 to drive thermogenic commitment

Area of Science:

• Metabolic Health
• Adipose Tissue Biology
• Thermogenesis

Background:

• Stimulating browning in white adipose tissue is a promising strategy for metabolic health improvement.
• The molecular mechanisms driving the differentiation of precursor cells into thermogenic adipocytes are not fully understood.

Purpose of the Study:

• To investigate the molecular determinants of thermogenic adipocyte differentiation.
• To identify key regulators involved in the browning of white adipose tissue.

Main Methods:

• Temporal high-resolution proteomic analysis of mouse subcutaneous white adipose tissue (scWAT) after cold exposure.
• Loss- and gain-of-function experiments (siRNA, CRISPRa) to assess the role of Y box-binding protein 1 (YBX1).
• Transcriptomic analysis to elucidate YBX1-controlled events during adipogenesis.

Main Results:

• Proteomics identified 509 differentially regulated proteins post-cold exposure, including YBX1 upregulation.
• YBX1 knockdown impaired thermogenic potential in preadipocytes.
• YBX1 induction in mesenchymal stem cells promoted browning, thermogenic marker expression, and mitochondrial respiration.
• YBX1 regulates genes like Jmjd1c to promote thermogenic adipocyte differentiation.

Conclusions:

• Dynamic proteomic changes in scWAT during browning were mapped.
• YBX1 was identified as a novel factor coordinating genomic mechanisms for brite/beige adipocyte lineage commitment.