Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet

Tsutomu Wada, Hiroki Kenmochi, Yusuke Miyashita, Motohiro Sasaki, Minoru Ojima, Masakiyo Sasahara, Daisuke Koya, Hiroshi Tsuneki, Toshiyasu Sasaoka*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

169 被引用数 (Scopus)

抄録

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

本文言語英語
ページ(範囲)2040-2049
ページ数10
ジャーナルEndocrinology
151
5
DOI
出版ステータス出版済み - 2010/05

ASJC Scopus 主題領域

  • 内分泌学

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