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2016-05-14 - Colloque/Article dans les actes avec comité de lecture - Anglais - 2 page(s)

Martin Blanche, Decleves Anne-Emilie , Colombaro V, Jadot Ines, Habsch Isabelle, Caron Nathalie, "EFFECTS OF INOS INHIBITION IN HIGH FAT DIET-INDUCED OBESITY" in 53rd ERA-EDTA Congress, Vienne, Autriche, 2016

  • Codes CREF : Sciences biomédicales (DI3200), Néphrologie - urologie (DI3325)
  • Unités de recherche UMONS : Biochimie métabolique et moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
  • Centres UMONS : Mind & Health (CREMH)
Texte intégral :

Abstract(s) :

(Anglais) Introduction and Aims: Obesity is aworldwide problem caused by caloric excess promoting deleterious cellular responses in organs. Endothelial dysfunction, impaired vasodilation and insulin resistance are considered as key features of obesity. Interactions between metabolic and hemodynamic factors activate intracellular signalling pathways, leading to the production of oxidative stress, pro-inflammatory cytokines and fibrotic factors. Among vasoactive factors, nitric oxide (NO) has been determined as playing acritical role in the pathogenesis of metabolic diseases. The aim of this study isto investigate the involvement of inducible nitric oxide synthase (iNOS) in the development of progressive renal dysfunction leading to obesity-induced kidney disease as well as in liverand adipose tissue. Methods: Todo so, C57BL/6 male micewererandomized to a low fat diet (LFD) ora high fat diet (HFD) and treated with pharmacological agent, L-NIL (iNOS inhibitor; 0.1 % in drinking water), for 16 weeks. Results: We have demonstrated thatiNOS inhibition with L-NIL prevented several changes in mice fed a HFD: increase of body weight, fasting blood glucose level and plasma levels of triglyceride, non-esterified fattyacids and insulin. Interestingly, the increase in albuminuria and mesangial matrix expansion were not ameliorated with L-NIL, while therewas a significant improvement in glycosuria and proteinuria. Moreover, the urinary hydrogen peroxidelevel, a stable product of ROS production, significantly higher in mice fed a HFD, wasreduced with L-NIL. To evaluate the beneficial effect of L-NIL in the development of insulin resistance, liverand peri-renal white adipose tissuewere also investigated. Histological analysis revealed an increasing size of adipocytes and an accumulation of lipid vacuoles into hepatocytes of mice fed a HFD along with increased liver triglyceride levelwhich were significantly decreased with L-NIL treatment. However, inflammation, as attested by macrophage infiltration and enhanced MCP-1 level, was only prevented by L-NIL in the adipose tissue but not in the liver. Conclusions: These results suggestthatinhibition of iNOS leadsto beneficial effects in kidney, especially in regard to tubular function. We also observed afavourable role of L-NIL administration in liverand adipose tissue of mice fed a HFD. However, further investigations are needed to better determine the role of iNOS in the targeted organs

(Anglais) Introduction and Aims: Obesity is aworldwide problem caused by caloric excess promoting deleterious cellular responses in organs. Endothelial dysfunction, impaired vasodilation and insulin resistance are considered as key features of obesity. Interactions between metabolic and hemodynamic factors activate intracellular signalling pathways, leading to the production of oxidative stress, pro-inflammatory cytokines and fibrotic factors. Among vasoactive factors, nitric oxide (NO) has been determined as playing acritical role in the pathogenesis of metabolic diseases. The aim of this study isto investigate the involvement of inducible nitric oxide synthase (iNOS) in the development of progressive renal dysfunction leading to obesity-induced kidney disease as well as in liverand adipose tissue. Methods: Todo so, C57BL/6 male micewererandomized to a low fat diet (LFD) ora high fat diet (HFD) and treated with pharmacological agent, L-NIL (iNOS inhibitor; 0.1 % in drinking water), for 16 weeks. Results: We have demonstrated thatiNOS inhibition with L-NIL prevented several changes in mice fed a HFD: increase of body weight, fasting blood glucose level and plasma levels of triglyceride, non-esterified fattyacids and insulin. Interestingly, the increase in albuminuria and mesangial matrix expansion were not ameliorated with L-NIL, while therewas a significant improvement in glycosuria and proteinuria. Moreover, the urinary hydrogen peroxidelevel, a stable product of ROS production, significantly higher in mice fed a HFD, wasreduced with L-NIL. To evaluate the beneficial effect of L-NIL in the development of insulin resistance, liverand peri-renal white adipose tissuewere also investigated. Histological analysis revealed an increasing size of adipocytes and an accumulation of lipid vacuoles into hepatocytes of mice fed a HFD along with increased liver triglyceride levelwhich were significantly decreased with L-NIL treatment. However, inflammation, as attested by macrophage infiltration and enhanced MCP-1 level, was only prevented by L-NIL in the adipose tissue but not in the liver. Conclusions: These results suggestthatinhibition of iNOS leadsto beneficial effects in kidney, especially in regard to tubular function. We also observed afavourable role of L-NIL administration in liverand adipose tissue of mice fed a HFD. However, further investigations are needed to better determine the role of iNOS in the targeted organs