Abstract
Extended food consumption during the rest period perturbs the phase relationship between circadian clocks in the periphery and the brain, leading to adverse health effects. Beyond the liver, how metabolic organs respond to a timed hypocaloric diet is largely unexplored. We investigated how feeding schedules impacted circadian gene expression in epididymal white and brown adipose tissue (eWAT and BAT) compared to the liver and hypothalamus. We restricted food to either daytime or nighttime in C57BL/6J male mice, with or without caloric restriction. Unlike the liver and eWAT, rhythmic clock genes in the BAT remained insensitive to feeding time, similar to the hypothalamus. We uncovered an internal split within the BAT in response to conflicting environmental cues, displaying inverted oscillations on a subset of metabolic genes without modifying its local core circadian machinery. Integrating tissue-specific responses on circadian transcriptional networks with metabolic outcomes may help elucidate the mechanism underlying the health burden of eating at unusual times.
| Original language | English (US) |
|---|---|
| Article number | 114523 |
| Journal | Cell reports |
| Volume | 43 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 27 2024 |
Funding
This research was supported by the Howard Hughes Medical Institute (J.S.T.), NIH/NIA grant R01 AG045795 (J.S.T. and C.B.G.), NIH/NIGMS R35 GM127122 (C.B.G.), NIH/NIGMS R00GM132557 (F.R.-F.), Milky Way Research Foundation MWRF210823 (J.S.T. and C.B.G.), NIDDK/1R01DK132647-01 (J.B.), NIDDK/R01DK090625 (J.B.), NIDDK/R01DK127800(J.B.), NIA/R01AG065988 (J.B.), and NIDDK/F32DK122675 (C.H.). We would like to thank Kimberly Brown, Delali Bassowou, and Victoria Ragland for assistance with animal care and maintenance, Izabela Kornblum for assistance in library preparations, and Dr. Shin Yamazaki for helpful discussions. J.S.T. is an investigator and F.R.-F. was a research associate at the Howard Hughes Medical Institute. Conceptualization, V.A.A.-R.; methodology, V.A.A.-R. and J.S.T.; investigation, V.A.A.-R. F.R.-F. L.v.R. M.I. C.J. J.S. and N.P.; visualization, V.A.A.-R.; funding acquisition, J.S.T. and C.B.G.; resources, J.B.; project administration, J.S.T. and C.B.G.; supervision, V.A.A.-R. J.S.T. and C.B.G.; writing \u2013 original draft, V.A.A.-R.; writing \u2013 review and editing, V.A.A.-R. J.S.T. C.B.G. J.B. L.v.R. F.R.-F. M.I. N.P. C.H. and A.K.T. All authors reviewed and approved the manuscript. The authors declare no competing interests. This research was supported by the Howard Hughes Medical Institute (J.S.T.), NIH/NIA grant R01 AG045795 (J.S.T. and C.B.G.), NIH/NIGMS R35 GM127122 (C.B.G.), NIH/NIGMS R00GM132557 (F.R.-F.), Milky Way Research Foundation MWRF210823 (J.S.T. and C.B.G.), NIDDK/1R01DK132647-01 (J.B.), NIDDK/R01DK090625 (J.B.), NIDDK/R01DK127800 (J.B.), NIA/R01AG065988 (J.B.), and NIDDK/F32DK122675 (C.H.). We would like to thank Kimberly Brown, Delali Bassowou, and Victoria Ragland for assistance with animal care and maintenance, Izabela Kornblum for assistance in library preparations, and Dr. Shin Yamazaki for helpful discussions. J.S.T. is an investigator and F.R.-F. was a research associate at the Howard Hughes Medical Institute.
Keywords
- brown adipose tissue
- caloric restriction
- circadian clocks
- CP: Metabolism
- dietary interventions
- liver
- misaligned feeding
- mouse behavior
- time-restricted feeding
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology