PMID- 31378798
OWN - NLM
STAT- MEDLINE
DCOM- 20200205
LR  - 20200205
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 10
IP  - 8
DP  - 2019 Aug 1
TI  - Ca(2+)-Calcineurin-NFAT pathway mediates the effect of thymol on oxidative 
      metabolism and fiber-type switch in skeletal muscle.
PG  - 5166-5173
LID - 10.1039/c8fo02248h [doi]
AB  - Thymol is a major component of thyme, and it has been reported that thymol 
      administration reduces body weight, plasma insulin and blood glucose in type-2 
      diabetes. Skeletal muscle is the most important metabolism organs in the body; 
      however, to date, there is no report on the effect of thymol on skeletal muscle. 
      Our goal was to determine whether thymol has an effect on the different types of 
      skeletal muscle fibers and their metabolism characteristics. Hence, we performed 
      in vivo and in vitro experiments. In vivo, SD rats (4 weeks old) were fed with 
      different concentrations of thymol for 4 weeks, and in vitro C2C12 myotubes were 
      directly treated with thymol for 2 days. The rats fed with 0.025% thymol showed a 
      significantly lower body weight, subcutaneous white adipose tissue index and 
      gastrocnemius muscle index (P < 0.05), while their proportion of brown adipose 
      tissue significantly increased (P < 0.05). The protein and mRNA expression of 
      MyHC I and MyHC IIa in the gastrocnemius muscle of the rats significantly 
      increased (P < 0.05), while the protein level of MyHC II and mRNA expression of 
      MyHC IIb decreased (P < 0.05). Furthermore, 0.025% thymol supplement 
      significantly reduced (P < 0.05) the activity of lactate dehydrogenase (LDH) in 
      the gastrocnemius muscle of the rats, but their succinate dehydrogenase (SDH) and 
      hexokinase (HK) activities increased (P < 0.05). Also, the expression of the 
      fatty acid oxidation-related genes in the gastrocnemius muscle of the rats 
      decreased with the thymol supplement (P < 0.05). In vitro, similar results were 
      obtained. Furthermore, the Ca(2+)-calcineurin-NFAT pathway, which is an important 
      pathway to regulate the transformation of skeletal muscle fiber type, was 
      studied. We found that the effects of thymol on the myosin heavy chain isoforms, 
      genes related to metabolism and the activation of the Ca(2+)-calcineurin-NFAT 
      pathway were all reversed by a Ca(2+) chelator (P < 0.05). Thus, thymol can 
      promote the oxidative metabolism and fiber type switch in skeletal muscle, and 
      the Ca(2+)-calcineurin-NFAT pathway plays an important role in it.
FAU - Luo, Pei
AU  - Luo P
AD  - Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of 
      Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, 
      People's Republic of China. qyjiang@scau.edu.cn.
FAU - Wang, Lina
AU  - Wang L
FAU - Luo, Lv
AU  - Luo L
FAU - Wang, Leshan
AU  - Wang L
FAU - Yang, Kelin
AU  - Yang K
FAU - Shu, Gang
AU  - Shu G
FAU - Wang, Songbo
AU  - Wang S
FAU - Zhu, Xiaotong
AU  - Zhu X
FAU - Gao, Ping
AU  - Gao P
FAU - Jiang, Qingyan
AU  - Jiang Q
LA  - eng
PT  - Journal Article
DEP - 20190805
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Plant Extracts)
RN  - 3J50XA376E (Thymol)
RN  - EC 3.1.3.16 (Calcineurin)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcineurin/genetics/*metabolism
MH  - Calcium/*metabolism
MH  - Cell Line
MH  - Male
MH  - Mice
MH  - Muscle Fibers, Skeletal/*drug effects/metabolism
MH  - Muscle, Skeletal/*drug effects/metabolism
MH  - Myosin Heavy Chains/genetics/metabolism
MH  - NFATC Transcription Factors/genetics/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Plant Extracts/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Thymol/*pharmacology
MH  - Thymus Plant/*chemistry
EDAT- 2019/08/06 06:00
MHDA- 2020/02/06 06:00
CRDT- 2019/08/06 06:00
PHST- 2019/08/06 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/08/06 06:00 [entrez]
AID - 10.1039/c8fo02248h [doi]
PST - ppublish
SO  - Food Funct. 2019 Aug 1;10(8):5166-5173. doi: 10.1039/c8fo02248h. Epub 2019 Aug 5.