Conditionally immortalized brown preadipocytes can switch between proliferative and differentiated states

Area of Science:

• Cell Biology
• Metabolic Research
• Adipose Tissue Biology

Background:

• Brown adipose tissue (BAT) is crucial for thermoregulation and metabolic health.
• Investigating human BAT is challenging due to limited cell availability and heterogeneity.
• Existing models often lack the ability to recapitulate key cellular processes.

Purpose of the Study:

• To generate and characterize conditionally immortalized brown preadipocytes (iBPAs) from human and mouse origins.
• To establish a versatile cell model for studying brown adipose tissue biology.
• To explore the potential of iBPAs in fundamental and applied research.

Main Methods:

• Conditional immortalization using a doxycycline-controlled Tet-On system expressing simian virus 40 large tumor antigen (LT).
• Generation of monoclonal cell lines from mouse and human brown preadipocytes.
• Induction of adipogenesis and assessment of brown adipocyte markers and functions.

Main Results:

• Both human and mouse iBPAs exhibited long-term proliferation under doxycycline induction.
• Differentiated iBPAs displayed key brown adipocyte characteristics, including lipid droplet accumulation and UCP1 expression.
• Human iBPAs required LT downregulation for adipogenesis, while mouse iBPAs showed plasticity, de-differentiating and proliferating again.

Conclusions:

• Conditionally immortalized brown preadipocytes (iBPAs) provide a robust and adaptable model for brown adipose tissue research.
• iBPAs facilitate the study of cellular and molecular mechanisms underlying BAT function and differentiation.
• The unique proliferative and differentiation capacity of iBPAs offers novel experimental avenues for metabolic disorder research.