The hepatic circadian clock is preserved in a lipid-induced mouse model of non-alcoholic steatohepatitis.
Recent studies have correlated metabolic diseases, such as metabolic syndrome and non-alcoholic fatty liver disease, with the circadian clock. However, whether such metabolic changes per se affect the circadian clock remains controversial. To address this, we investigated the daily mRNA expression profiles of clock genes in the liver of a dietary mouse model of non-alcoholic steatohepatitis (NASH) using a custom-made, high-precision DNA chip. C57BL/6J mice fed an atherogenic diet for 5 weeks developed hypercholesterolemia, oxidative stress, and NASH. DNA chip analyses revealed that the atherogenic diet had a great influence on the mRNA expression of a wide range of genes linked to mitochondrial energy production, redox regulation, and carbohydrate and lipid metabolism. However, the rhythmic mRNA expression of the clock genes in the liver remained intact. Most of the circadianly expressed genes also showed 24-h rhythmicity. These findings suggest that the biological clock is protected against such a metabolic derangement as NASH.
Ando
Hitoshi
H
Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan.
Takamura
Toshinari
T
Matsuzawa-Nagata
Naoto
N
Shima
Kosuke R
KR
Nakamura
Seiji
S
Kumazaki
Masafumi
M
Kurita
Seiichiro
S
Misu
Hirofumi
H
Togawa
Naoyuki
N
Fukushima
Tatsunobu
T
Fujimura
Akio
A
Kaneko
Shuichi
S
D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics / Q000503:physiopathology*; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis