TNF-α and IL-6 Induces Caspase and Inhibits BCL2 in Human Adipose Tissue: A Potential Relationship with Obesity and the Onset of Insulin Resistance (original) (raw)

Diabetes Care

Abstract

OBJECTIVE: Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS: The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-a or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In...

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