PMID- 33290156
OWN - NLM
STAT- MEDLINE
DCOM- 20211222
LR  - 20211222
IS  - 1205-7541 (Electronic)
IS  - 0008-4212 (Linking)
VI  - 99
IP  - 8
DP  - 2021 Aug
TI  - Theobromine ameliorates nonalcoholic fatty liver disease by regulating hepatic 
      lipid metabolism via mTOR signaling pathway in vivo and in vitro.
PG  - 775-785
LID - 10.1139/cjpp-2020-0259 [doi]
AB  - Theobromine, a methylxanthine present in cocoa, has been shown to possess many 
      beneficial pharmacological properties such as anti-oxidative stress, 
      anti-inflammatory property, and anti-microbial activity. In this study, we 
      investigated the effects of theobromine on nonalcoholic fatty liver disease 
      (NAFLD) and the possible underlying mechanisms in vivo and in vitro. The results 
      showed that theobromine reduced body weight and fat mass and improved 
      dyslipidemia. Theobromine mitigated liver injury and significantly reduced 
      hepatic triglyceride level in mice with obesity. Histological examinations also 
      showed hepatic steatosis was alleviated after theobromine treatment. Furthermore, 
      theobromine reversed the elevated mRNA and protein expression of SREBP-1c, FASN, 
      CD36, FABP4, and the suppressed expression of PPARalpha and CPT1a in the liver of 
      mice with obesity, which were responsible for lipogenesis, fatty acid uptake, and 
      fatty acid oxidation respectively. In vitro, theobromine also downregulated 
      SREBP-1c, FASN, CD36, FABP4 and upregulated PPARalpha and CPT1a mRNA and protein 
      levels in hepatocytes in a dose-dependent manner, while these changes were 
      reversed by L-leucine, a mammalian target of rapamycin (mTOR) agonist. The 
      present study demonstrated that theobromine improved NAFLD by inhibiting 
      lipogenesis and fatty acid uptake and promoting fatty acid oxidation in the liver 
      and hepatocytes, which might be associated with its suppression of mTOR signaling 
      pathway. Novelty: Theobromine protects against high-fat diet - induced NAFLD. 
      Theobromine inhibits lipogenesis and fatty acid uptake and promotes fatty acid 
      oxidation in the liver and hepatocytes via inhibiting mTOR signaling pathway.
FAU - Wei, Dan
AU  - Wei D
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Shandong First Medical University, Jinan, Shandong, China.
FAU - Wu, Shaofei
AU  - Wu S
AD  - Department of Hepatology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan, Shandong, China.
FAU - Liu, Jie
AU  - Liu J
AD  - Department of Public Health, Tengzhou Central People's Hospital, Zaozhuang, 
      Shandong, China.
FAU - Zhang, Xiaoqian
AU  - Zhang X
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Shandong First Medical University, Jinan, Shandong, China.
FAU - Guan, Xiaoling
AU  - Guan X
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Shandong First Medical University, Jinan, Shandong, China.
FAU - Gao, Li
AU  - Gao L
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Shandong First Medical University, Jinan, Shandong, China.
FAU - Xu, Zhipeng
AU  - Xu Z
AD  - Department of Urology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan, Shandong, China.
LA  - eng
PT  - Journal Article
DEP - 20201208
PL  - Canada
TA  - Can J Physiol Pharmacol
JT  - Canadian journal of physiology and pharmacology
JID - 0372712
SB  - IM
MH  - Animals
MH  - Lipogenesis
MH  - Male
MH  - Mice
MH  - *Non-alcoholic Fatty Liver Disease
OTO - NOTNLM
OT  - fatty acid oxidation
OT  - fatty acid uptake
OT  - lipogenesis
OT  - lipogenese
OT  - mTOR
OT  - mobilisation des acides gras
OT  - nonalcoholic fatty liver disease
OT  - oxydation des acides gras
OT  - steatose hepatique non alcoolique
OT  - theobromine
OT  - theobromine
EDAT- 2020/12/09 06:00
MHDA- 2021/12/24 06:00
CRDT- 2020/12/08 17:13
PHST- 2020/12/09 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2020/12/08 17:13 [entrez]
AID - 10.1139/cjpp-2020-0259 [doi]
PST - ppublish
SO  - Can J Physiol Pharmacol. 2021 Aug;99(8):775-785. doi: 10.1139/cjpp-2020-0259. 
      Epub 2020 Dec 8.