Irisin: A Possible Marker of Adipose Tissue Dysfunction in Obesity

Adipose tissue (AT) secretes pro- and anti-inflammatory cytokines involved in AT homeostasis, including tumor necrosis factor-& alpha; (TNF & alpha;) and irisin. The functionality of AT is based on a regulated equilibrium between adipogenesis and extracellular matrix (ECM) remodeling. We investigated the contributions of adipose progenitors (ASCs) and adipocytes (AMCs) to TNF & alpha;-induced ECM remodeling and a possible implication of irisin in AT impairment in obesity. ASCs and AMCs were exposed to TNF & alpha; treatment and nuclear factor-kappa (NF-kB) pathway was investigated: Tissue Inhibitor of Metalloproteinase (TIMP-1), Twist Family Transcription Factor 1 (TWIST-1), and peroxisome proliferator-activated receptor-& gamma; (PPAR & gamma;) expression levels were analyzed. The proteolytic activity of matrix metalloproteinases (MMPs) -2 and -9 was analyzed by zymography, and the irisin protein content was measured by ELISA. In inflamed AMCs, a TIMP-1/TWIST-1 imbalance leads to a drop in PPAR & gamma;. Adipogenesis and lipid storage ability impairment come with local tissue remodeling due to MMP-9 overactivation. In vitro and ex vivo measurements confirm positive correlations among inflammation, adipose secreting irisin levels, and circulating irisin levels in patients with visceral obesity. Our findings identify the NF-kB downstream effectors as molecular initiators of AT dysfunction and suggest irisin as a possible AT damage and obesity predictive factor.

Automated summary

This study investigated the contributions of adipose progenitors (ASCs) and adipocytes (AMCs) to TNF-alpha-induced extracellular matrix (ECM) remodeling and the potential involvement of irisin in AT impairment in obesity. The results showed that inflamed adipocytes exhibited impaired protein metabolism and lipid storage ability, accompanied by increased matrix metalloproteinase activity. In vitro and ex vivo measurements revealed a positive correlation between inflammation, adipose secretion of irisin, and circulating irisin levels in patients with visceral obesity.