AFF4 regulates cellular adipogenic differentiation via targeting autophagy

Area of Science:

• Molecular Biology
• Cell Biology
• Metabolic Research

Background:

• Transcriptional elongation, regulated by the super elongation complex (SEC), is vital for gene expression.
• SEC dysregulation is linked to human diseases, but its developmental and homeostatic roles are unclear.
• AFF4 (AF4/FMR2 family member 4) is an essential scaffold protein for SEC assembly and stability.

Purpose of the Study:

• To investigate the physiological role of SEC, specifically AFF4, in adipogenesis (fat cell formation).
• To elucidate the molecular mechanisms by which AFF4 influences adipogenesis.

Main Methods:

• Knockdown and overexpression of AFF4 in human mesenchymal stem cells (hMSCs) and 3T3-L1 preadipocytes.
• Generation of adipose-specific Aff4 knockout mice using Fabp4-cre driver.
• Analysis of adipogenic differentiation, autophagy markers (ATG5, ATG16L1), and gene transcription.

Main Results:

• AFF4 knockdown inhibited adipogenesis in cell models; AFF4 overexpression enhanced it.
• Adipose-specific AFF4 deficiency in mice impaired adipocyte development and white fat depot formation.
• AFF4 directly regulates autophagy by promoting the transcription of ATG5 and ATG16L1.

Conclusions:

• AFF4 plays a critical role in regulating autophagy during adipogenesis.
• AFF4 is essential for adipocyte development and white adipose tissue formation.
• These findings expand the understanding of transcriptional regulation in adipogenesis.