Regular feeding plays an important role in cholesterol homeostasis through the liver circadian clock.
BACKGROUND
Peripheral clock control and the relevance of the circadian rhythm to physiology and disease are major questions in mammalian circadian biology.


OBJECTIVE
We examined the physiological functions of the liver clock.


RESULTS
We established a suppressed feeding schedule regimen constituting a high-cholesterol diet delivered every 6 hours without changes in energy and cholesterol intake. We found that rats exposed to this regimen developed hypercholesteremia. In the liver, the rhythmicity of expression of several clock genes was disrupted. Furthermore, the nocturnal expression of the CYP7A1 gene, which encodes the rate-limiting enzyme for the conversion of cholesterol to bile acids, was shifted to a diurnal pattern. Indeed, suppression of a regular feeding rhythm increased the secretion rate of very-low-density lipoprotein cholesterol from the liver and decreased the excretion of fecal bile acids.


CONCLUSIONS
Our results demonstrated that not only the amount and quality of food but also the timing of meals has crucial health implications.
Yamajuku
Daisuke
D
Department of Applied Molecular Biosciences, Laboratory of Nutritional Biochemistry, Nagoya University, Nagoya 464-8601, Japan.
Okubo
Shingo
S
Haruma
Tomonori
T
Inagaki
Takahiko
T
Okuda
Yuji
Y
Kojima
Tomoko
T
Noutomi
Keiji
K
Hashimoto
Seiichi
S
Oda
Hiroaki
H
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000378:metabolism*; D002940:Circadian Rhythm; D004036:Diet, Atherogenic; D005248:Feeding Methods; D006706:Homeostasis; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*
D001647:Bile Acids and Salts; D015243:Cholesterol, VLDL; D013254:Steroid 17-alpha-Hydroxylase