Potential mechanism of hepatic lipid accumulation during a long-term rest phase restricted feeding in mice

ABSTRACT

Eating during a rest phase disrupts the biological clock system and leads to obesity and metabolic diseases. Although a rest phase restricted feeding (RF) is reported to enhance hepatic lipid accumulation, the mechanism(s) of the phenomenon is still unknown. This study evaluated the potential involvement of the CD36-related transport of lipids into the liver in mice with the RF procedure. This study showed that hepatic lipid accumulation was more significant in the RF group compared with mice under an active phase restricted feeding (AF). The RF procedure also elevated the expression of CD36 mRNA and its protein on the cellular membrane throughout the day. The transcription factor profiling array revealed that the RF activated the proliferator-activated receptor-γ (PPARγ), one of the CD36 transcript enhancers. In the liver of RF mice, the expression of miR-27b-3p, which is known to interfere with PPARγ gene expression, significantly decreased. These results suggest that the RF procedure inhibits the expression of miR-27b-3p in the liver and subsequently elevates PPARγ activity. Activated PPARγ might lead to CD36 upregulation, which, in turn, stimulates the transport of lipids into the liver.

KEYWORDS:

• Restricted feeding
• hepatic lipid accumulation
• miR-27b-3p
• PPARγ
• CD36

Acknowledgements

This work was supported by KAKENHI Grant-in-Aid for Young Scientists [20K19715] to Y.T., KAKENHI Grant-in-Aid for Research Activity Start-up [19K23832] to Y.T. and KAKENHI Grant-in-Aid for Fundamental Research(C) [19K23832, 20K19715] to Y.T].

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

All authors (Y.T., T.A., M.H., Y.W., A.F. and K.U.) participated in designing the study, interpreted the data and contributed to the writing and/or revising of the manuscript. Y.T., T.A., Y.W. and K.U. performed research, and Y.T. and K.U. performed data analysis.

Additional information

Funding

This work was supported by the JSPS [19K07327,19K23832,20K19715].