GDF15 (Growth/Differentiation Factor-15) Expression in Human Adipose Tissue and in Adipocyte Cell Lines

Area of Science:

• Endocrinology
• Immunology
• Metabolic Research

Background:

• Growth/differentiation factor-15 (GDF15) is a stress-induced gene within the TGF-β family.
• GDF15 may play a role in metaflammation and adipoflammation.
• Its regulation in adipocytes and adipose tissue (AT) by immune and metabolic factors is not fully understood.

Purpose of the Study:

• To investigate the regulation of GDF15 in adipocytes and adipose tissue.
• To examine the effects of Toll-like receptor (TLR) activation, hypoxia, and metabolic factors on GDF15.

Main Methods:

• GDF15 mRNA and protein levels were measured in human SGBS cells, human visceral (VAT) and subcutaneous adipose tissue (SAT), and murine 3T3-L1 adipocytes.
• Stimuli included insulin, glucose, TLR ligands, bile acids, FXR/TGR5 activators, and HIF1α activators.
• Quantification used real-time RT-PCR and ELISA.

Main Results:

• GDF15 expression in human SAT and VAT positively correlated with serum GDF15 levels in obese patients.
• Insulin and ursodeoxycholic acid (bile acid) upregulated GDF15 in 3T3-L1 adipocytes via FXR.
• TLR7 activation and hypoxia upregulated GDF15, while STAT3 signaling downregulated it.

Conclusions:

• Adipose tissue GDF15 expression correlates with circulating levels and is influenced by metabolic and innate immune pathways.
• These pathways are implicated in adipose tissue inflammation and metaflammation.
• GDF15 regulation offers potential insights into obesity-related inflammatory processes.