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Long term treatment with ACE inhibitor enalapril decreases body weight gain and increases life span in rats
Authors:Edson Lucas Santos,Elton Dias da Silva,Paulo J. Forcina Martins,Joã  o Bosco Pesquero
Affiliation:a School of Environmental and Biological Science, Federal University of Grande Dourados, Rodovia dourados - Itahum, Km 12, Dourados, MS, Brazil
b Department of Biophysics, Federal University of São Paulo, Rua Botucatu 862/7o. andar, Vila Clementino, 04023-062 São Paulo, SP, Brazil
c Department of Psychobiology, Federal University of São Paulo, São Paulo, SP, Brazil
Abstract:Renin-angiotensin system is involved in homeostasis processes linked to renal and cardiovascular system and recently has been linked to metabolic syndrome. We analyzed the influence of long term angiotensin I converting enzyme (ACE) inhibitor enalapril treatment in normotensive adult Wistar rats fed with standard or palatable hyperlipidic diets. Our results show that long term enalapril treatment decreases absolute food intake, serum leptin concentration and body weight gain. Moreover, in adipose tissue, enalapril treatment led to decreased ACE activity, enhanced the expression of peroxisome proliferator activated receptor gamma, adiponectin, hormone-sensitive lipase, fatty acid synthase, catalase and superoxide dismutase resulting in prolonged life span. On the other hand, the ACE inhibitor was not able to improve the transport of leptin through the blood brain barrier or to alter the sensitivity of this hormone in the central nervous system. The effect of enalapril in decreasing body weight gain was also observed in older rats. In summary, these results extend our previous findings and corroborate data from the literature regarding the beneficial metabolic effects of enalapril and show for the first time that this ACE inhibitor prolongs life span in rats also fed with palatable hyperlipidic diet, an action probably correlated with adipose tissue metabolic modulation and body weight reduction.
Keywords:AngII, angiotensin II   ACE, angiotensin converting enzyme   ACEi, ACE inhibitors   FAS, fatty acid synthase   GLUT4, glucose transporter-4   GPX, glutathione peroxidase   HSL, hormone-sensive lipase   icv, intracerebroventricular   PPARγ, peroxisome proliferator activated receptor gamma   RAS, renin-angiotensin system   AT1, receptor type 1   Cu/Zn-SOD, copper/zinc-superoxide dismutase   Mn-SOD, manganese-superoxide dismutase
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