Send to

Choose Destination
PLoS One. 2018 Oct 31;13(10):e0206669. doi: 10.1371/journal.pone.0206669. eCollection 2018.

Delayed first active-phase meal, a breakfast-skipping model, led to increased body weight and shifted the circadian oscillation of the hepatic clock and lipid metabolism-related genes in rats fed a high-fat diet.

Author information

Laboratory of Nutritional Biochemistry, Nagoya University, Nagoya, Japan.
Department of Nutritional Sciences, Nagoya University of Arts and Sciences, Nisshin, Japan.
Institute of Innovation for Future Society, Nagoya University, Nagoya, Japan.
Faculty of Education, Oita University, Oita, Japan.


The circadian clock is closely related to human health, such as metabolic syndrome and cardiovascular disease. Our previous study revealed that irregular feeding induced abnormal lipid metabolism with disruption of the hepatic circadian clock. We hypothesized that breakfast skipping induces lipid abnormalities, such as adiposity, by altering the hepatic circadian oscillation of clock and lipid metabolism-related genes. Here, we established a delayed first active-phase meal (DFAM) protocol as a breakfast-skipping model. Briefly, rats were fed a high-fat diet during zeitgeber time (ZT) 12-24 in a control group and ZT 16-4 in the DFAM group. The DFAM group showed increased body weight gain and perirenal adipose tissue weight without a change in total food intake. The circadian oscillations of hepatic clock and de novo fatty acid synthesis genes were delayed by 2-4 h because of DFAM. The peaks of serum insulin, a synchronizer for the liver clock, bile acids, and non-esterified fatty acid (NEFA) were delayed by 4-6 h because of DFAM. Moreover, DFAM delayed the surge in body temperature by 4 h and may have contributed to the increase in body weight gain and adipose tissue weight because of decreased energy expenditure. These data indicated a potential molecular mechanism by which breakfast skipping induces abnormal lipid metabolism, which is related to the altered circadian oscillation of hepatic gene expression. The results also suggested that the delayed peaks of serum NEFA, bile acids, and insulin entrain the circadian rhythm of hepatic clock and lipid metabolism-related genes.

Conflict of interest statement

The authors have declared that no competing interests exist.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center