Increased IL-32 Levels in Obesity Promote Adipose Tissue Inflammation and Extracellular Matrix Remodeling. Effect of Weight Loss

ABSTRACT

Interleukin (IL)-32 is a recently described cytokine involved in the regulation of inflammation. We aimed to explore whether IL-32 could function as an inflammatory and angiogenic factor in human obesity and obesity-associated type 2 diabetes.

Samples obtained from 90 subjects were used in the study. We show, for the first time that increased circulating levels of IL-32 in obese patients decreased after weight loss achieved by Roux-en-Y gastric bypass but not following a conventional hypocaloric diet.

Obese patients exhibited higher expression levels of IL-32 in visceral adipose tissue (AT) as well as in subcutaneous AT and peripheral mononuclear blood cells. IL32 was mainly expressed by stromovascular fraction cells, and its expression was significantly enhanced by inflammatory stimuli and hypoxia, while no changes were found after the incubation with anti-inflammatory cytokines.

The addition of exogenous IL-32 induced the expression of inflammation and extracellular matrix-related genes in human adipocyte cultures and IL32-silenced adipocytes showed a downregulation of inflammatory genes.

Furthermore, adipocyte-conditioned media obtained from obese patients increased IL32 gene expression in human monocyte cultures, whereas the adipocyte-conditioned media from lean volunteers had no effect on IL32 mRNA levels.

These findings provide evidence, for the first time, about the inflammatory and remodeling properties of IL-32 in AT implicating this cytokine in obesity-associated comorbidities.

CITATION  Diabetes. 2016 Sep 14. pii: db160287