Study of the effects of monacolin k and other constituents of red yeast rice on obesity, insulin-resistance, hyperlipidemia, and nonalcoholic steatohepatitis using a mouse model of metabolic syndrome

Abstract

Purpose. Nonalcoholic fatty liver disease (NAFLD) is a progressive and intractable disease associated with metabolic syndrome. Red yeast rice (RYR) contains monacolin K, a potent inhibitor of HMG-CoA reductase, and its consumption decreases cholesterol and triglyceride levels. We examined the efficacy of RYR constituents using a novel metabolic syndrome-NAFLD mouse model (MSG mice). Methods. Two types of RYR grown under different culture conditions were used. 1P-DU contained only 0.002 g/100 g of monacolin K, whereas 3P-D1 contained 0.131 g/100 g. MSG mice were divided into three groups: control (C) group fed standard food, RYR-C group fed standard food with 1% 1P-DU, and RYR-M group fed standard food with 1% 3P-D1. Mice were examined from 12 to 24 weeks of age. Results. Serum insulin, leptin, and liver damage as well as macrophage aggregation in visceral fat in RYR-C and RYR-M groups were lower than those in C group. The serum adiponectin levels in RYR-C group were significantly higher than those in RYR-M and C groups. Conclusions. RYR was effective against obesity-related inflammation, insulin resistance, and NAFLD in MSG mice irrespective of monacolin K levels. GABA and various peptides produced during fermentation were determined as the active constituents of RYR.

Figure 1

Glucose (a), insulin (b), leptin (c), and adiponectin (d) levels at 24 weeks of age in all experimental groups. All mice were administered MSG at birth. Variables are expressed as mean ± SEM. *P < 0.05; **P < 0.01.

Figure 2

HE and oil red O staining of the liver tissue in all experimental groups. NAS was calculated after HE staining (100x) at 24 weeks in all experimental groups. All mice were administered MSG at birth. Representative tissue staining images are illustrated. Variables are expressed as mean ± SEM. Representative tissue staining images are illustrated. *P < 0.05; **P < 0.01.

Figure 3

IL-6 and TNF-α immunohistochemical staining of the liver tissue and visceral fat at 24 weeks of age in all experimental groups. All mice were administered MSG at birth. Representative tissue staining images are illustrated. Scale bar means 100 μm.

Figure 4

CYP2E1, α-SMA, and CD31 immunohistochemical staining and TUNEL staining of the liver tissue at 24 weeks of age in all experimental groups. All mice were administered MSG at birth. Representative tissue staining images are illustrated.

Figure 5

The number of adipocytes and CLSs was determined after HE staining of visceral fat at 24 weeks in the three experimental groups. All mice were administered MSG at birth. Representative tissue staining images are illustrated. CLS is illustrated by arrow. Representative tissue staining images are illustrated. Variables are expressed as mean ± SEM. **P < 0.01.