PMID- 29727630
OWN - NLM
STAT- MEDLINE
DCOM- 20190220
LR  - 20190320
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Linking)
VI  - 85
DP  - 2018 Aug
TI  - Theacrine protects against nonalcoholic fatty liver disease by regulating 
      acylcarnitine metabolism.
PG  - 227-239
LID - S0026-0495(18)30117-3 [pii]
LID - 10.1016/j.metabol.2018.04.011 [doi]
AB  - 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.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Wang, Guo-En
AU  - Wang GE
AD  - 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.
FAU - Li, Yi-Fang
AU  - Li YF
AD  - 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.
FAU - Zhai, Yu-Jia
AU  - Zhai YJ
AD  - 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.
FAU - Gong, Lian
AU  - Gong L
AD  - 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.
FAU - Tian, Jing-Yu
AU  - Tian JY
AD  - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer 
      Center, Guangzhou 510060, Guangdong, China.
FAU - Hong, Mo
AU  - Hong M
AD  - 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.
FAU - Yao, Nan
AU  - Yao N
AD  - 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.
FAU - Wu, Yan-Ping
AU  - Wu YP
AD  - 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.
FAU - Kurihara, Hiroshi
AU  - Kurihara H
AD  - 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.
FAU - He, Rong-Rong
AU  - He RR
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180501
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Apolipoproteins E)
RN  - 0 (Plant Extracts)
RN  - 0 (Protective Agents)
RN  - 0 (acylcarnitine)
RN  - 268B43MJ25 (Uric Acid)
RN  - 2UMI9U37CP (Oleic Acid)
RN  - EJ939L81MY (1,3,7,9-tetramethyluric acid)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/genetics/metabolism
MH  - Carnitine/*analogs & derivatives/metabolism
MH  - Diet, High-Fat/adverse effects
MH  - Energy Metabolism/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/metabolism
MH  - Oleic Acid
MH  - Plant Extracts/pharmacology/*therapeutic use
MH  - Protective Agents/pharmacology/*therapeutic use
MH  - Signal Transduction/drug effects
MH  - Uric Acid/*analogs & derivatives/pharmacology/therapeutic use
OTO - NOTNLM
OT  - Deacetylation
OT  - Hepatic steatosis
OT  - Long-chain acyl coenzyme A dehydrogenase
OT  - SIRT3
EDAT- 2018/05/05 06:00
MHDA- 2019/03/21 06:00
CRDT- 2018/05/05 06:00
PHST- 2017/11/21 00:00 [received]
PHST- 2018/04/27 00:00 [revised]
PHST- 2018/04/29 00:00 [accepted]
PHST- 2018/05/05 06:00 [pubmed]
PHST- 2019/03/21 06:00 [medline]
PHST- 2018/05/05 06:00 [entrez]
AID - S0026-0495(18)30117-3 [pii]
AID - 10.1016/j.metabol.2018.04.011 [doi]
PST - ppublish
SO  - Metabolism. 2018 Aug;85:227-239. doi: 10.1016/j.metabol.2018.04.011. Epub 2018 
      May 1.