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Eburicoic Acid, a Triterpenoid Compound from Antrodia camphorata, Displays Antidiabetic and Antihyperlipidemic Effects in Palmitate-Treated C2C12 Myotubes and in High-Fat Diet-Fed Mice.
Int J Mol Sci 2017; 18(11)IJ

Abstract

This study was designed to investigate the antidiabetic and antihyperlipidemic effects and mechanisms of eburicoic acid (TRR); one component of Antrodia camphorata in vitro and in an animal model for 14 weeks. Expression levels of membrane glucose transporter type 4 (GLUT4); phospho-5'-adenosine monophosphate-activated protein kinase (AMPK)/total AMPK; and phospho-Akt/total-Akt in insulin-resistant C2C12 myotube cells were significantly decreased by palmitate; and such decrease was prevented and restored by TRR at different concentrations. A group of control (CON) was on low-fat diet over a period of 14 weeks. Diabetic mice; after high-fat-diet (HFD) induction for 10 weeks; were randomly divided into six groups and were given once a day oral gavage doses of either TRR (at three dosage levels); fenofibrate (Feno) (at 0.25 g/kg body weight); metformin (Metf) (at 0.3 g/kg body weight); or vehicle (distilled water) (HF group) over a period of 4 weeks and still on HFD. Levels of glucose; triglyceride; free fatty acid (FFA); insulin; and leptin in blood were increased in 14-week HFD-fed mice as compared to the CON group; and the increases were prevented by TRR, Feno, or Metf as compared to the HF group. Moreover, HFD-induction displayed a decrease in circulating adiponectin levels, and the decrease was prevented by TRR, Feno, or Metf treatment. The overall effect of TRR is to decrease glucose and triglyceride levels and improved peripheral insulin sensitivity. Eburicoic acid, Feno, and Metf displayed both enhanced expression levels of phospho-AMPK and membrane expression levels of GLUT4 in the skeletal muscle of HFD-fed mice to facilitate glucose uptake with consequent enhanced hepatic expression levels of phospho-AMPK in the liver and phosphorylation of the transcription factor forkhead box protein O1 (FOXO1) but decreased messenger RNA (mRNA) of phosphenolpyruvate carboxykinase (PEPCK) to inhibit hepatic glucose production; resulting in lowered blood glucose levels. Moreover; TRR treatment increased hepatic expression levels of the peroxisome proliferator-activated receptor α (PPARα) to enhance fatty acid oxidation; but displayed a reduction in expressions of hepatic fatty acid synthase (FAS) but an increase in fatty acid oxidation PPARα coincident with a decrease in hepatic mRNA levels of sterol response element binding protein-1c (SREBP-1c); resulting in a decrease in blood triglycerides and amelioration of hepatic ballooning degeneration. Eburicoic acid-treated mice reduced adipose expression levels of lipogenic FAS and peroxisome proliferator-activated receptor γ (PPARγ) and led to decreased adipose lipid accumulation. The present findings demonstrated that TRR exhibits a beneficial therapeutic potential in the treatment of type 2 diabetes and hyperlipidemia.

Authors+Show Affiliations

Department of Internal Medicine, Fengyuan Hospital, Ministry of Health and Welfare, Fengyuan District, Taichung City 42055, Taiwan. keny71@pchome.com.tw.Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung City 40402, Taiwan. kuoyh@mail.cmu.edu.tw. Department of Biotechnology, Asia University, Taichung 41354, Taiwan. kuoyh@mail.cmu.edu.tw.Graduate Institute of Biotechnology and Biomedical Engineering, College of Health Science, Central Taiwan University of Science and Technology, No.666 Buzih Road, Beitun District, Taichung City 40601, Taiwan. ccshih@ctust.edu.tw.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29099085

Citation

Lin, Cheng-Hsiu, et al. "Eburicoic Acid, a Triterpenoid Compound From Antrodia Camphorata, Displays Antidiabetic and Antihyperlipidemic Effects in Palmitate-Treated C2C12 Myotubes and in High-Fat Diet-Fed Mice." International Journal of Molecular Sciences, vol. 18, no. 11, 2017.
Lin CH, Kuo YH, Shih CC. Eburicoic Acid, a Triterpenoid Compound from Antrodia camphorata, Displays Antidiabetic and Antihyperlipidemic Effects in Palmitate-Treated C2C12 Myotubes and in High-Fat Diet-Fed Mice. Int J Mol Sci. 2017;18(11).
Lin, C. H., Kuo, Y. H., & Shih, C. C. (2017). Eburicoic Acid, a Triterpenoid Compound from Antrodia camphorata, Displays Antidiabetic and Antihyperlipidemic Effects in Palmitate-Treated C2C12 Myotubes and in High-Fat Diet-Fed Mice. International Journal of Molecular Sciences, 18(11), doi:10.3390/ijms18112314.
Lin CH, Kuo YH, Shih CC. Eburicoic Acid, a Triterpenoid Compound From Antrodia Camphorata, Displays Antidiabetic and Antihyperlipidemic Effects in Palmitate-Treated C2C12 Myotubes and in High-Fat Diet-Fed Mice. Int J Mol Sci. 2017 Nov 2;18(11) PubMed PMID: 29099085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eburicoic Acid, a Triterpenoid Compound from Antrodia camphorata, Displays Antidiabetic and Antihyperlipidemic Effects in Palmitate-Treated C2C12 Myotubes and in High-Fat Diet-Fed Mice. AU - Lin,Cheng-Hsiu, AU - Kuo,Yueh-Hsiung, AU - Shih,Chun-Ching, Y1 - 2017/11/02/ PY - 2017/10/04/received PY - 2017/10/26/revised PY - 2017/10/28/accepted PY - 2017/11/4/entrez PY - 2017/11/4/pubmed PY - 2018/6/21/medline KW - Antrodia camphorata KW - diabetes KW - eburicoic acid KW - fatty acid synthase KW - forkhead box protein O1 KW - peroxisome proliferator-activated receptor α JF - International journal of molecular sciences JO - Int J Mol Sci VL - 18 IS - 11 N2 - This study was designed to investigate the antidiabetic and antihyperlipidemic effects and mechanisms of eburicoic acid (TRR); one component of Antrodia camphorata in vitro and in an animal model for 14 weeks. Expression levels of membrane glucose transporter type 4 (GLUT4); phospho-5'-adenosine monophosphate-activated protein kinase (AMPK)/total AMPK; and phospho-Akt/total-Akt in insulin-resistant C2C12 myotube cells were significantly decreased by palmitate; and such decrease was prevented and restored by TRR at different concentrations. A group of control (CON) was on low-fat diet over a period of 14 weeks. Diabetic mice; after high-fat-diet (HFD) induction for 10 weeks; were randomly divided into six groups and were given once a day oral gavage doses of either TRR (at three dosage levels); fenofibrate (Feno) (at 0.25 g/kg body weight); metformin (Metf) (at 0.3 g/kg body weight); or vehicle (distilled water) (HF group) over a period of 4 weeks and still on HFD. Levels of glucose; triglyceride; free fatty acid (FFA); insulin; and leptin in blood were increased in 14-week HFD-fed mice as compared to the CON group; and the increases were prevented by TRR, Feno, or Metf as compared to the HF group. Moreover, HFD-induction displayed a decrease in circulating adiponectin levels, and the decrease was prevented by TRR, Feno, or Metf treatment. The overall effect of TRR is to decrease glucose and triglyceride levels and improved peripheral insulin sensitivity. Eburicoic acid, Feno, and Metf displayed both enhanced expression levels of phospho-AMPK and membrane expression levels of GLUT4 in the skeletal muscle of HFD-fed mice to facilitate glucose uptake with consequent enhanced hepatic expression levels of phospho-AMPK in the liver and phosphorylation of the transcription factor forkhead box protein O1 (FOXO1) but decreased messenger RNA (mRNA) of phosphenolpyruvate carboxykinase (PEPCK) to inhibit hepatic glucose production; resulting in lowered blood glucose levels. Moreover; TRR treatment increased hepatic expression levels of the peroxisome proliferator-activated receptor α (PPARα) to enhance fatty acid oxidation; but displayed a reduction in expressions of hepatic fatty acid synthase (FAS) but an increase in fatty acid oxidation PPARα coincident with a decrease in hepatic mRNA levels of sterol response element binding protein-1c (SREBP-1c); resulting in a decrease in blood triglycerides and amelioration of hepatic ballooning degeneration. Eburicoic acid-treated mice reduced adipose expression levels of lipogenic FAS and peroxisome proliferator-activated receptor γ (PPARγ) and led to decreased adipose lipid accumulation. The present findings demonstrated that TRR exhibits a beneficial therapeutic potential in the treatment of type 2 diabetes and hyperlipidemia. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/29099085/Eburicoic_Acid_a_Triterpenoid_Compound_from_Antrodia_camphorata_Displays_Antidiabetic_and_Antihyperlipidemic_Effects_in_Palmitate_Treated_C2C12_Myotubes_and_in_High_Fat_Diet_Fed_Mice_ L2 - http://www.mdpi.com/resolver?pii=ijms18112314 DB - PRIME DP - Unbound Medicine ER -