Extracellular matrix (ECM) remodeling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX) family of amine oxidases, including LOX and LOX-like (LOXL) isoenzymes, controls ECM maturation, and up-regulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. We have observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression was strongly up-regulated in samples from obese patients referred to bariatric surgery. LOX expression was also induced in the adipose tissue from male Wistar rats fed a high fat diet (HFD). Interestingly, treatment with β-aminopropionitrile (BAPN), a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content observed in adipose tissue from obese animals and improved several metabolic parameters: ameliorated glucose and insulin levels, decreased HOMA index and reduced plasma triglyceride levels. Furthermore, in white adipose tissue from obese animals, BAPN prevented the downregulation of adiponectin and glucose transporter 4 (GLUT4), and the increase in suppressor of cytokine signaling 3 (SOCS3) and dipeptidyl peptidase 4 (DPP4) levels, triggered by the HFD. Likewise, in the TNFα-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalized insulin-stimulated glucose uptake. Therefore, our data evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasize the interest of novel pharmacological interventions targeting adipose tissue fibrosis and LOX activity for the clinical management of this disease.
- Received January 20, 2015.
- Accepted March 28, 2015.
- © 2015. Published by The Company of Biologists Ltd
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