TNFalpha up-regulates apelin expression in human and mouse adipose tissue

Area of Science:

• Metabolic research
• Adipose tissue biology
• Inflammation and obesity

Background:

• Apelin is a novel adipokine influenced by insulin and obesity.
• Obesity and insulin resistance correlate with elevated insulin and TNFα levels.
• The role of TNFα in regulating apelin expression in adipocytes is not fully understood.

Purpose of the Study:

• To investigate the regulation of apelin expression in adipocytes by TNFα.
• To explore the relationship between apelin and TNFα in human adipose tissue.
• To elucidate the signaling pathways involved in TNFα-induced apelin expression.

Main Methods:

• Analysis of apelin and TNFα expression in human adipose tissue from lean and obese individuals.
• Studies using cultured human adipose tissue explants and differentiated 3T3F442A adipocytes.
• In vivo experiments in C57Bl6/J mice involving TNFα injection.
• Investigation of signaling pathways including PI3-kinase, JNK, and MAPK.

Main Results:

• A strong correlation between apelin and TNFα expression was observed in human adipose tissue.
• Endogenous TNFα in adipocytes increased apelin expression, an effect reversed by TNFα inhibition.
• Obese mice showed increased adipocyte expression of both TNFα and apelin.
• TNFα administration in mice elevated apelin expression in adipose tissue and plasma levels.
• TNFα directly stimulated apelin expression and secretion in 3T3F442A adipocytes via PI3-kinase, JNK, and MAPK pathways.

Conclusions:

• TNFα positively regulates apelin expression and secretion in adipocytes.
• Apelin may serve as a molecular link between obesity, inflammation, and insulin resistance.
• These findings provide a basis for understanding obesity-related metabolic disorders.