Adipose inflammation at the heart of vascular disease

Area of Science:

• Cardiovascular Biology
• Metabolic Disease Research
• Molecular Mechanisms of Inflammation

Background:

• Visceral adipose tissue (VAT) is a key inflammatory site in obesity, linked to atherosclerotic vascular disease.
• Molecular pathways mediating VAT's contribution to systemic inflammation remain incompletely understood.
• Identifying secretory pathways is crucial for understanding obesity-associated cardiovascular risks.

Purpose of the Study:

• To investigate the role of c-Jun NH2 terminal kinase (JNK) signaling in VAT.
• To elucidate the JNK-driven secretory pathway involving adipocyte fatty acid binding protein (A-FABP) in atherosclerosis.
• To determine if targeting JNK in VAT can mitigate atherosclerosis progression.

Main Methods:

• Utilized a transgenic mouse model with adipose tissue-specific dominant-negative JNK (dnJNK) expression.
• Examined atherosclerosis development in ApoE-/- mice with modified VAT.
• Performed transplantation studies using visceral adipose tissue with inactivated JNK.

Main Results:

• JNK-driven A-FABP expression in VAT exacerbates atherosclerosis in ApoE-/- mice.
• Mice receiving VAT with inactivated JNK showed reduced systemic inflammation.
• Transplantation of JNK-inactivated VAT significantly decreased atherosclerosis compared to controls.

Conclusions:

• Visceral adipose tissue acts as a secretory organ influencing systemic disease.
• The JNK/A-FABP pathway in VAT is critical for adipose-vascular cross-talk.
• Targeting JNK in visceral fat offers a potential therapeutic strategy against atherosclerosis.