Spironolactone Improves Glucose and Lipid Metabolism by Ameliorating Hepatic Steatosis and Inflammation and Suppressing Enhanced Gluconeogenesis Induced by High-Fat and High-Fructose Diet

• DOI: 10.1210/en.2009-0869
• Publication Date: 2010-04-21T17:38:56Z
• Authors: Tsutomu Wada; Hiroki Kenmochi; Yusuke Miyashita; Motohiro Sasaki; Minoru Ojima; Masakiyo Sasahara; Daisuke Koya; Hiroshi Tsuneki; Toshiyasu Sasaoka
• Keywords: Inflammation; Male; 2. Zero hunger; 0301 basic medicine; Body Weight; Gluconeogenesis; Gene Expression; Hep G2 Cells; Lipid Metabolism; Dietary Fats; Lipids; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Fatty Liver; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Glucose; Dietary Carbohydrates; Animals; Humans; Insulin; Cells, Cultured; Mineralocorticoid Receptor Antagonists

Recent evidence suggests that treatment with mineralocorticoid receptor antagonist suppressed local inflammation in vascular tissues or cardiomyocytes; therefore, we examined the effect of spironolactone on glucose and lipid metabolism a mouse model diet-induced diabetes nonalcoholic fatty liver disease. C57BL/6 mice were fed either control diet, 60% fat diet 30% fructose water (HFFD), HFFD for 8 wk. demonstrated apparent phenotypes metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, liver. Although did not affect increased calorie intake body weight by HFFD, increments epididymal weight, blood pressure, serum triglyceride, free acids, leptin, total cholesterol levels significantly suppressed. Elevation during tolerance tests was lowered spironolactone. Notably, pyruvate test almost completely ameliorated to treatment. Staining hematoxylin-eosin (HE) Oil-red-O marked accumulation triglycerides centrilobular part hepatic lobule mice, these accumulations effectively improved Concomitantly feeding markedly up-regulated mRNA expression proinflammatory cytokines (TNFα, IL-6, monocyte chemoattractant protein-1), gluconeogenic gene phosphoenolpyruvate carboxykinase, transcription factor carbohydrate response element binding protein, its downstream lipogenic enzymes, all which These results indicate inhibition might be beneficial therapeutic approach syndrome