Elevated Endoplasmic Reticulum Stress Response Contributes to Adipose Tissue Inflammation in Aging

Area of Science:

• Cell Biology
• Immunology
• Metabolic Disease Research

Background:

• Adipose tissue inflammation is linked to age-related metabolic diseases, but mechanisms remain unclear.
• Aberrant endoplasmic reticulum (ER) stress is correlated with inflammation and insulin resistance in diet-induced obesity.

Purpose of the Study:

• To investigate if increased ER stress response contributes to age-associated adipose tissue inflammation.
• To determine if chemical chaperones can mitigate ER stress and inflammation in aging adipose tissue.

Main Methods:

• Compared ER stress markers in adipose tissue from young and old mice.
• Assessed sensitivity of aged stromal cells and macrophages to ER stress inducers.
• Treated cells and aged mice with the chemical chaperone 4-phenylbutyric acid (4-PBA).

Main Results:

• Old mice showed elevated ER stress markers (BIP, CHOP, cleaved-ATF-6, phospho-IRE1α, XBP-1) in adipose tissue.
• Aged stromal cells and macrophages exhibited increased ER stress and inflammatory cytokine production (IL-6, MCP-1, TNF-α).
• 4-PBA treatment alleviated ER stress and reduced inflammatory markers in both young and old mice, and in aged mice fed 4-PBA.

Conclusions:

• Exaggerated ER stress in aging adipose tissue drives age-associated inflammation.
• Chemical chaperones offer a potential therapeutic strategy to mitigate age-related adipose tissue inflammation.