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1,8-Cineole Ameliorates Steatosis of Pten Liver Specific KO Mice via Akt Inactivation.

Murata S, Ogawa K, Matsuzaka T, Chiba M, Nakayama K, Iwasaki K, Kurokawa T, Sano N, Tanoi T, Ohkohchi N - Int J Mol Sci (2015)

Bottom Line: At eight weeks, livers from each group were processed to measure triglyceride (TG) content, gene expression analysis, western blot analysis, and histological examination including Oil red O staining. 1,8-cineole ameliorated hepatic steatosis in Pten KO mice, revealed by TG content and Oil red O staining.Moreover, 1,8-cineole downregulated collagen 1a1 expression and improved liver fibrosis.Thus, 1,8-cineole has potential as a candidate to treat NASH by inactivating the Akt/PI3-kinase pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. soichiro@md.tsukuba.ac.jp.

ABSTRACT
Hepatocyte-specific Phosphatase and tensin homolog (Pten)-knockout (KO) mice exhibit hepatic lesions analogous to non-alcoholic steatohepatitis (NASH). 1,8-cineole is a monoterpene oxide and it has several biological effects including hepatoprotective effects. In this study we revealed that 1,8-cineole ameliorates NASH of Pten KO mice. Pten KO mice were assigned to a control group without any medication or to a 1,8-cineole group injected with 50 mg/kg i.p. twice per week for eight weeks. At eight weeks, livers from each group were processed to measure triglyceride (TG) content, gene expression analysis, western blot analysis, and histological examination including Oil red O staining. 1,8-cineole ameliorated hepatic steatosis in Pten KO mice, revealed by TG content and Oil red O staining. Moreover, 1,8-cineole downregulated collagen 1a1 expression and improved liver fibrosis. Thus, 1,8-cineole has potential as a candidate to treat NASH by inactivating the Akt/PI3-kinase pathway.

No MeSH data available.


Related in: MedlinePlus

(a) Western blot of fatty acid synthase (FASN), phospho Akt (P-Akt), total Akt (T-Akt), phospho mTOR (P-mTOR), total mTOR (mTOR), Phospho-protein phosphatase type 2A (P-PP2A), total PP2A (PP2A), phospho-insulin receptor (P-insulin receptor), total insulin receptor (insulin receptor) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the 1,8-cineole group, FASN, P-Akt, P-mTOR, and P-PP2A were decreased. P-insulin receptor was increased in the 1,8-cineole group. Densitometry of FASN/GAPDH (b), phospho/total Akt (c), phospho/total mTOR (d), phospho/total PP2A (e), and phospho/total insulin receptor (f) in the two groups (n = 3). In the 1,8-cineole group, Akt and PP2A were significantly dephosphorylated, and the insulin receptor was significantly activated. *p < 0.05 vs. control.
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ijms-16-12051-f002: (a) Western blot of fatty acid synthase (FASN), phospho Akt (P-Akt), total Akt (T-Akt), phospho mTOR (P-mTOR), total mTOR (mTOR), Phospho-protein phosphatase type 2A (P-PP2A), total PP2A (PP2A), phospho-insulin receptor (P-insulin receptor), total insulin receptor (insulin receptor) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the 1,8-cineole group, FASN, P-Akt, P-mTOR, and P-PP2A were decreased. P-insulin receptor was increased in the 1,8-cineole group. Densitometry of FASN/GAPDH (b), phospho/total Akt (c), phospho/total mTOR (d), phospho/total PP2A (e), and phospho/total insulin receptor (f) in the two groups (n = 3). In the 1,8-cineole group, Akt and PP2A were significantly dephosphorylated, and the insulin receptor was significantly activated. *p < 0.05 vs. control.

Mentions: Figure 2a shows a western blot of the liver of the control and 1,8-cineole groups. In the 1,8-cineole group, FASN, phospho Akt, phospho mTOR were decreased compared to the control. The phospho-insulin receptor was strongly activated in the 1,8-cineole group. Densitometry of FASN/GAPDH (Figure 2b), phospho/total Akt (Figure 2c), phospho/total mTOR (Figure 2d), phospho/total PP2A (Figure 2e), and phospho/total insulin receptor (Figure 2f) in the two groups are shown. In the 1,8-cineole group, Akt and PP2A were significantly dephosphorylated, and the insulin receptor was significantly activated compared to the control group. FASN and phospho mTOR expression were also decreased in the 1,8-cineole group without significant difference.


1,8-Cineole Ameliorates Steatosis of Pten Liver Specific KO Mice via Akt Inactivation.

Murata S, Ogawa K, Matsuzaka T, Chiba M, Nakayama K, Iwasaki K, Kurokawa T, Sano N, Tanoi T, Ohkohchi N - Int J Mol Sci (2015)

(a) Western blot of fatty acid synthase (FASN), phospho Akt (P-Akt), total Akt (T-Akt), phospho mTOR (P-mTOR), total mTOR (mTOR), Phospho-protein phosphatase type 2A (P-PP2A), total PP2A (PP2A), phospho-insulin receptor (P-insulin receptor), total insulin receptor (insulin receptor) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the 1,8-cineole group, FASN, P-Akt, P-mTOR, and P-PP2A were decreased. P-insulin receptor was increased in the 1,8-cineole group. Densitometry of FASN/GAPDH (b), phospho/total Akt (c), phospho/total mTOR (d), phospho/total PP2A (e), and phospho/total insulin receptor (f) in the two groups (n = 3). In the 1,8-cineole group, Akt and PP2A were significantly dephosphorylated, and the insulin receptor was significantly activated. *p < 0.05 vs. control.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4490428&req=5

ijms-16-12051-f002: (a) Western blot of fatty acid synthase (FASN), phospho Akt (P-Akt), total Akt (T-Akt), phospho mTOR (P-mTOR), total mTOR (mTOR), Phospho-protein phosphatase type 2A (P-PP2A), total PP2A (PP2A), phospho-insulin receptor (P-insulin receptor), total insulin receptor (insulin receptor) and Glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the 1,8-cineole group, FASN, P-Akt, P-mTOR, and P-PP2A were decreased. P-insulin receptor was increased in the 1,8-cineole group. Densitometry of FASN/GAPDH (b), phospho/total Akt (c), phospho/total mTOR (d), phospho/total PP2A (e), and phospho/total insulin receptor (f) in the two groups (n = 3). In the 1,8-cineole group, Akt and PP2A were significantly dephosphorylated, and the insulin receptor was significantly activated. *p < 0.05 vs. control.
Mentions: Figure 2a shows a western blot of the liver of the control and 1,8-cineole groups. In the 1,8-cineole group, FASN, phospho Akt, phospho mTOR were decreased compared to the control. The phospho-insulin receptor was strongly activated in the 1,8-cineole group. Densitometry of FASN/GAPDH (Figure 2b), phospho/total Akt (Figure 2c), phospho/total mTOR (Figure 2d), phospho/total PP2A (Figure 2e), and phospho/total insulin receptor (Figure 2f) in the two groups are shown. In the 1,8-cineole group, Akt and PP2A were significantly dephosphorylated, and the insulin receptor was significantly activated compared to the control group. FASN and phospho mTOR expression were also decreased in the 1,8-cineole group without significant difference.

Bottom Line: At eight weeks, livers from each group were processed to measure triglyceride (TG) content, gene expression analysis, western blot analysis, and histological examination including Oil red O staining. 1,8-cineole ameliorated hepatic steatosis in Pten KO mice, revealed by TG content and Oil red O staining.Moreover, 1,8-cineole downregulated collagen 1a1 expression and improved liver fibrosis.Thus, 1,8-cineole has potential as a candidate to treat NASH by inactivating the Akt/PI3-kinase pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. soichiro@md.tsukuba.ac.jp.

ABSTRACT
Hepatocyte-specific Phosphatase and tensin homolog (Pten)-knockout (KO) mice exhibit hepatic lesions analogous to non-alcoholic steatohepatitis (NASH). 1,8-cineole is a monoterpene oxide and it has several biological effects including hepatoprotective effects. In this study we revealed that 1,8-cineole ameliorates NASH of Pten KO mice. Pten KO mice were assigned to a control group without any medication or to a 1,8-cineole group injected with 50 mg/kg i.p. twice per week for eight weeks. At eight weeks, livers from each group were processed to measure triglyceride (TG) content, gene expression analysis, western blot analysis, and histological examination including Oil red O staining. 1,8-cineole ameliorated hepatic steatosis in Pten KO mice, revealed by TG content and Oil red O staining. Moreover, 1,8-cineole downregulated collagen 1a1 expression and improved liver fibrosis. Thus, 1,8-cineole has potential as a candidate to treat NASH by inactivating the Akt/PI3-kinase pathway.

No MeSH data available.


Related in: MedlinePlus