Abstract
The finding that animals with circadian gene mutations exhibit diet-induced obesity and metabolic syndrome with hypoinsulinemia revealed a distinct role for the clock in the brain and peripheral tissues. Obesogenic diets disrupt rhythmic sleep/wake patterns, feeding behavior, and transcriptional networks, showing that metabolic signals reciprocally control the clock. Providing access to high-fat diet only during the sleep phase (light period) in mice accelerates weight gain, whereas isocaloric time-restricted feeding during the active period enhances energy expenditure due to circadian induction of adipose thermogenesis. This perspective focuses on advances and unanswered questions in understanding the interorgan circadian control of healthful metabolism.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 655-669 |
| Number of pages | 15 |
| Journal | Cell Metabolism |
| Volume | 36 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2 2024 |
Funding
I wish to especially thank Kate Moynihan Ramsey for meticulous reading and suggestions and Billie Marcheva for help with the figures. I also thank Chelsea Hepler, Jonathan Cedaernes, Ben Weidemann, and Clara Bien Peek for their thoughtful comments, in addition to all present and past lab members whose work has been instrumental throughout our studies. Special thanks also to my colleagues Grant Barish, Lisa Beutler, and Nav Chandel for innumerable insights and input. Research support was from the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01DK127800 , R01DK113011 , R01DK090625 , and R01DK050203 ; the National Institute on Aging (NIA) grants R01AG065988 and P01AG011412 ; and the University of Chicago Diabetes Research and Training Center grant P30DK020595 .
Keywords
- circadian
- diabetes
- epigenetics
- insulin
- metabolism
- molecular clock
- obesity
- sleep
- thermogenesis
- transcription
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cell Biology
