Spironolactone prevents dietary-induced metabolic syndrome by inhibiting PI3-K/Akt and p38MAPK signaling pathways

• Published in: Journal of endocrinological investigation Vol. 36; no. 11; pp. 923 - 930
• Main Authors: Long, H.-D., Lin, Y.-E., Liu, M.-J., Liang, L.-Y., Zeng, Z.-H.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2013
• Subjects: Aldosterone - biosynthesis; Animals; Apoptosis - drug effects; Diet, High-Fat - adverse effects; Dyslipidemias - prevention & control; Endocrinology; Hypertension - prevention & control; Insulin-Secreting Cells - drug effects; Male; MAP Kinase Signaling System - drug effects; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic Syndrome - prevention & control; Original Article; Phosphatidylinositol 3-Kinases - physiology; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Rats; Rats, Wistar; Receptors, Mineralocorticoid - biosynthesis; Sodium Chloride, Dietary - adverse effects; Spironolactone - therapeutic use; mitogen-activated protein kinase; phosphatidylinositol 3-kinase/Akt; Metabolic syndrome; spironolactone; aldosterone
• ISSN: 0391-4097; 1720-8386
• DOI: 10.3275/8946

Objectives: Aim of the study is to evaluate the impact of spironolactone (SPL) on indexes of metabolic syndrome (MS) and further investigate the mechanisms underlying its protective effects. Methods: A rat model of MS was established by administering a fat- and salt-enriched diet (FS diet). The occurrence of MS was examined by measurement of blood pressure (BP), aldosterone (ALD) content, blood lipid (BL), glucose and insulin levels. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Pancreatic gland tissue injury was assessed by β-cell apoptosis. Mineralocorticoid receptor (MR) activity, phosphatidylinositol 3-kinase/Akt (PI3-K/Akt), and phosphorylation of p38MAPK (P-p38MAPK) in pancreatic gland tissue were evaluated by western blot analysis. Results: SPL prevented hypertension, and dyslipidemia during MS induced by the intake of FS diet, but had no effect on K + and Na + disturbances. Furthermore, SPL significantly attenuated ALD and MR expression levels after FS diet. Finally, SPL inhibited phosphorylation protein kinase B (p-PKB) activation in the pancreatic gland tissue, a downstream target of PI3-K, and phosphorylation of p38MAPK pathway, critical for cellular apoptosis. Conclusions: This study demonstrates that SPL exerts a protective effect on hypertension and dyslipidemia. This protective effect may depend, at least in part, on MAPK and PI3-K pathways.