Xin MA, Jiaojiao SHI, Ka CHEN, et al. Dihydromyricetin improves rhythm disorder in expression of liver circadian clock genes in non-alcoholic fatty liver mice[J]. Journal of Third Military Medical University, 2018, 40(21): 1956-1961.
DOI:
Xin MA, Jiaojiao SHI, Ka CHEN, et al. Dihydromyricetin improves rhythm disorder in expression of liver circadian clock genes in non-alcoholic fatty liver mice[J]. Journal of Third Military Medical University, 2018, 40(21): 1956-1961. DOI: 10.16016/j.1000-5404.201805085.
Dihydromyricetin improves rhythm disorder in expression of liver circadian clock genes in non-alcoholic fatty liver mice
摘要
Abstract
Objective
2
To investigate the possible role of circadian rhythm variation of hepatic clock-related genes in the improvement of hepatic lipid metabolism in high-fat diet (HFD)-induced mice after dihydromyricetin (DHM) treatment.
Methods
2
A total of 150 C57BL/6J male mice (6 weeks old) were randomly divided into normal diet group (CON)
HFD group and HFD+DHM treatment [100 mg/(kg·d)] group. After 12 weeks of intervention
the liver tissues of mice were stained with oil O red
and the liver triglyceride levels were detected. The hepatocytes of each group were extracted at ZT18 and ZT6 by a two-step perfusion method according to the Zeitgeber time (ZT0 represents the light time point at 8:00 am). The oxygen consumption rate (OCR) was detected immediately. The liver tissues were also harvested at ZT0
ZT4
ZT8
ZT12
ZT16 and ZT20
respectively. The mRNA and protein expression levels of hepatic clock-related genes
circadian locomotor output cycles kaput (CLOCK)
brain and muscle-arnt-like 1 (BMAL1)
and Period2 (PER2) were detected by real-time PCR and Western blot analysis.
Results
2
The HFD group presented dominant accumulation of fat droplets in the interstitial space after oil O red staining and increased triglyceride content in the liver tissues (
P
<
0.05)
and significantly reduced basic OCR and maximum respiratory OCR level at the ZT18 and ZT6 (
P
<
0.05) when compared with the CON group. HFD feeding led to significantly decreased expression of CLOKC and BMAL1 at mRNA and protein levels at ZT0
ZT4
ZT8 and ZT20
and to that of PER2 at ZT4
ZT8
ZT16 and ZT20 in liver tissues (
P
<
0.05). Furthermore
DHM treatment significantly inhibited HFD-induced fat accumulation and hepatic triglyceride elevation as well as the decreased levels of the basis OCR and maximal respiratory OCR at ZT18 and ZT6 in the hepatocyte
s (with that of ZT18 significantly higher than that of ZT6). Besides
it also significantly antagonized HFD-induced changes of mRNA and protein expression of CLOCK.
Conclusion
2
DHM partially reverses the rhythm disorder of the expression of liver clock-related genes in non-alcoholic fatty liver disease mice
and thereby improves hepatic lipid metabolism.
关键词
Keywords
references
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Related Author
Xin MA
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Related Institution
Department of Rehabilitation Medicine, General Hospital of Chengdu Military Command
Research Center of Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Center of Medical Nutrition, Institute of Military Preventive Medicine, Third Military Medical University
Department of Gastroenterology,People’s Hospital of Chongqing Hechuan
Department of Gastroenterology, Chongqing Key Laboratory of Precise Prevention and Treatment of Digestive Malignancies, Daping Hospital, Army Medical University
College of Pharmaceutical Sciences, Southwest University