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Metabolism. 2018 Aug;85:227-239. doi: 10.1016/j.metabol.2018.04.011. Epub 2018 May 1.

Theacrine protects against nonalcoholic fatty liver disease by regulating acylcarnitine metabolism.

Author information

1
Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
2
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.
3
Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou 510095, China.
4
Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. Electronic address: rongronghe@jnu.edu.cn.

Abstract

OBJECTIVE:

Acylcarnitine metabolism disorder contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). There are, however, few ideal medications for NAFLD, which work by targeting acylcarnitine metabolism. The aim of this study was to investigate the protective effects of theacrine, a rare purine alkaloid isolated from Camellia assamica var. kucha, against acylcarnitine metabolism disorder in NAFLD.

METHODS:

The pharmacological activities of theacrine were studied using high-fat diet (HFD)-fed ApoE-/- and C57BL/6J mice models. Oleate-treated HepG2 and L-02 cells were used to investigate the molecular mechanism of theacrine on acylcarnitine metabolism. The target of theacrine was confirmed in vitro as the blockade of sirtuin 3 (SIRT3) and protein kinase A.

RESULTS:

Theacrine inhibits hepatic steatosis and liver inflammation and improves energy expenditure in HFD-fed mice. Theacrine ameliorates acylcarnitine metabolism disorder in HFD-fed mice and oleate-treated hepatocytes by improving fatty acid oxidation. The underlying mechanism involves theacrine's activation of the mitochondrial deacetylase SIRT3 and consequently, the increased activity of long-chain acyl coenzyme A dehydrogenase (LCAD) through deacetylation.

CONCLUSION:

Theacrine promotes acylcarnitine metabolism in NAFLD through the SIRT3/LCAD signaling pathway. The target of theacrine's activities on NAFLD is identified as SIRT3.

KEYWORDS:

Deacetylation; Hepatic steatosis; Long-chain acyl coenzyme A dehydrogenase; SIRT3

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