PMID- 33071780
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201022
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - Slow-Release H(2)S Donor Anethole Dithiolethione Protects Liver From Lipotoxicity 
      by Improving Fatty Acid Metabolism.
PG  - 549377
LID - 10.3389/fphar.2020.549377 [doi]
LID - 549377
AB  - "Lipotoxicity" induced by free fatty acids (FAs) plays a central role in the 
      pathogenesis of many metabolic diseases, with few treatment options available 
      today. Hydrogen sulfide (H(2)S), a novel gaseous signaling molecule, has been 
      reported to have a variety of pharmacological properties, but its effect on FAs 
      metabolism remains unclear. The purpose of this study was to investigate the 
      effect and mechanisms of anethole dithiolethione (ADT, a sustained-release H(2)S 
      donor) on hepatic FAs metabolism. ADT was administered daily for 4 weeks in male 
      Syrian golden hamsters fed a high fat diet (HFD), and FAs profiles of liver 
      tissues were analyzed using GC-MS. The results showed that in HFD-fed hamsters, 
      ADT treatment significantly reduced the accumulation of toxic saturated and 
      monounsaturated fatty acids (C16:0, C18:0, C16:1, and C18:1n9), while increased 
      the content of n-6 and n-3 series polyunsaturated fatty acids (C20:3n6, C20:4n6, 
      and C22:6n3). Mechanistically, ADT obviously inhibited the overexpression of 
      acetyl-CoA carboxylase1 (ACC1), fatty acid synthase (FAS), and stearoyl-CoA 
      desaturase1 (SCD1), and up-regulated the levels of fatty acid transport proteins 
      (FATPs), liver fatty acid binding protein (L-FABP), carnitine 
      palmitoyltransferase 1alpha (CPT1alpha), fatty acid desaturase (FADS)1 and FADS2. 
      Notably, ADT administration significantly promoted Mitofusin1-mediated 
      mitochondrial fusion and fatty acid beta-oxidation. These findings suggest that ADT 
      plays a beneficial role by regulating the synthesis, desaturation, beta-oxidation, 
      uptake, binding/isolation, and transport of FAs. In conclusion, ADT is effective 
      in improving FAs metabolic disorders and liver injuries caused by HFD, which 
      renders ADT a candidate drug for lipotoxicity-induced diseases.
CI  - Copyright (c) 2020 Zhao, Yu, Li, Cai, Liu, Hu, Liu and Tang.
FAU - Zhao, Chengcheng
AU  - Zhao C
AD  - Department of Pharmacy, The Second Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Institute of Clinical Pharmacy, Central South University, Changsha, China.
FAU - Yu, Nannan
AU  - Yu N
AD  - Department of Pharmacy, The Second Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Institute of Clinical Pharmacy, Central South University, Changsha, China.
FAU - Li, Wenqun
AU  - Li W
AD  - Department of Pharmacy, The Second Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Institute of Clinical Pharmacy, Central South University, Changsha, China.
FAU - Cai, Hualin
AU  - Cai H
AD  - Department of Pharmacy, The Second Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Institute of Clinical Pharmacy, Central South University, Changsha, China.
FAU - Liu, Mouze
AU  - Liu M
AD  - Department of Pharmacy, The Second Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Institute of Clinical Pharmacy, Central South University, Changsha, China.
FAU - Hu, Yanjie
AU  - Hu Y
AD  - Department of Stomatology, Suiyang County People's Hospital, Zunyi, China.
FAU - Liu, Yiping
AU  - Liu Y
AD  - Department of Pharmacy, The Second Xiangya Hospital, Central South University, 
      Changsha, China.
AD  - Institute of Clinical Pharmacy, Central South University, Changsha, China.
FAU - Tang, Mimi
AU  - Tang M
AD  - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 
      China.
AD  - Institute for Rational and Safe Medication Practices, National Clinical Research 
      Center for Geriatric Disorders, Xiangya Hospital, Central South University, 
      Changsha, China.
LA  - eng
PT  - Journal Article
DEP - 20200923
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7538629
OTO - NOTNLM
OT  - fatty acid beta-oxidation
OT  - hydrogen sulfide
OT  - lipotoxicity
OT  - liver injuries
OT  - oleic acid
OT  - palmitic acid
EDAT- 2020/10/20 06:00
MHDA- 2020/10/20 06:01
PMCR- 2020/09/23
CRDT- 2020/10/19 05:54
PHST- 2020/04/06 00:00 [received]
PHST- 2020/09/02 00:00 [accepted]
PHST- 2020/10/19 05:54 [entrez]
PHST- 2020/10/20 06:00 [pubmed]
PHST- 2020/10/20 06:01 [medline]
PHST- 2020/09/23 00:00 [pmc-release]
AID - 10.3389/fphar.2020.549377 [doi]
PST - epublish
SO  - Front Pharmacol. 2020 Sep 23;11:549377. doi: 10.3389/fphar.2020.549377. 
      eCollection 2020.