The lysyl oxidase inhibitor beta-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats
Por:
Miana, M, Galan, M, Martinez-Martinez, E, Varona, S, Jurado-Lopez, R, Bausa-Miranda, B, Antequera, A, Luaces, M, Martinez-Gonzalez, J, Rodriguez, C, Cachofeiro, V
Publicada:
1 jun 2015
Resumen:
Extracellular matrix (ECM) remodelling 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 upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression is strongly upregulated in samples from obese individuals that had been 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 beta-aminopropionitrile (BAPN), a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass that was observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content that was observed in adipose tissue from obese animals and improved several metabolic parameters - it ameliorated glucose and insulin levels, decreased homeostasis model assessment (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), as well as the increase in suppressor of cytokine signaling 3 (SOCS3) and dipeptidyl peptidase 4 (DPP4) levels, triggered by the HFD. Likewise, in the TNF alpha-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalised insulin-stimulated glucose uptake. Therefore, our data provide evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasise the interest of novel pharmacological interventions that target adipose tissue fibrosis and LOX activity for the clinical management of this disease.
Filiaciones:
Miana, M:
Univ Complutense, Fac Med, Dept Fisiol, E-28040 Madrid, Spain
IiSGM, Madrid 28007, Spain
Galan, M:
CSIC, IIB St Pau, ICCC, Ctr Invest Cardiovasc, Barcelona 08025, Spain
Martinez-Martinez, E:
Univ Complutense, Fac Med, Dept Fisiol, E-28040 Madrid, Spain
IiSGM, Madrid 28007, Spain
NavarraBiomed Fdn Miguel Servet, Cardiovasc Translat Res, Pamplona 31008, Spain
Varona, S:
CSIC, IIB St Pau, ICCC, Ctr Invest Cardiovasc, Barcelona 08025, Spain
Jurado-Lopez, R:
Univ Complutense, Fac Med, Dept Fisiol, E-28040 Madrid, Spain
IiSGM, Madrid 28007, Spain
Bausa-Miranda, B:
Univ Complutense, Fac Med, Dept Fisiol, E-28040 Madrid, Spain
IiSGM, Madrid 28007, Spain
Antequera, A:
Fuenlabrada Univ Hosp, Upper Gastroenterol & Bariatr Surg Dept, Madrid 28942, Spain
Luaces, M:
Hosp Clin San Carlos, Cardiovasc Inst, Dept Cardiol, Madrid 28040, Spain
Martinez-Gonzalez, J:
CSIC, IIB St Pau, ICCC, Ctr Invest Cardiovasc, Barcelona 08025, Spain
Rodriguez, C:
CSIC, IIB St Pau, ICCC, Ctr Invest Cardiovasc, Barcelona 08025, Spain
Cachofeiro, V:
Univ Complutense, Fac Med, Dept Fisiol, E-28040 Madrid, Spain
IiSGM, Madrid 28007, Spain
Gold, Green Published
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