en
Doctoral thesis
Open access
English

SIRT1 in SF1 neurons links light inputs to circadian function in skeletal muscle

ContributorsAras, Ebru
Defense date2019-04-09
Abstract

Organismal homeostasis relies on the complex feedback communication and interaction between central nervous system and peripheral metabolic tissues. The mammalian circadian system coordinates the communication of many physiological aspects, including metabolism, in synchrony with the daily environmental changes throughout the 24h rotation of the Earth. Failure in the communication between environmental changes, central nervous system and peripheral clocks can desynchronize circadian system and contribute to development of diseases such as insulin resistance and diabetes. Hypothalamic nuclei reside at the top of this communication hierarchy and light inputs are conveyed to suprachiasmatic nucleus (SCN) of the hypothalamus. However, the circuitry of how SCN is linked and relays information to coordinate the diurnal oscillations to peripheral tissues is not clear. Here, we identify a key role SIRT1 in steroidogenic factor 1 (SF1) neurons of the ventromedial hypothalamic nucleus (VMH) in relaying light information to regulate skeletal muscle circadian function. We showed that insulin sensitivity of several metabolic tissues fluctuates during the day, which is lowest during the light period and at its highest during the dark period in mice. Mechanistically, we demonstrated that mice lacking SIRT1 in SF1 neurons are able to convey feeding inputs to, but are insensitive to the effects of light in reshaping the circadian transcriptome and insulin sensitivity in skeletal muscle. While this mutation does not affect the clocks in the SCN and VMH, it selectively governs the circadian function in gastrocnemius. These findings reveal a light, SF1 neurons and skeletal muscle axis that regulates the skeletal muscle insulin sensitivity and circadian function.

eng
Keywords
  • Skeletal muscle
  • Gastrocnemius
  • Glucose metabolism
  • Insulin signaling
  • Insulin sensitivity
  • Insulin resistance
  • Circadian rhythm
  • Light
  • Sirtuin
  • SIRT1
  • SF1 neurons
  • Ventromedial hypothalamus
  • VMH
  • Suprachiasmatic nucleus
  • SCN
Citation (ISO format)
ARAS, Ebru. SIRT1 in SF1 neurons links light inputs to circadian function in skeletal muscle. 2019. doi: 10.13097/archive-ouverte/unige:125022
Main files (1)
Thesis
accessLevelPublic
Identifiers
686views
90downloads

Technical informations

Creation10/16/2019 3:21:00 PM
First validation10/16/2019 3:21:00 PM
Update time03/15/2023 6:14:38 PM
Status update03/15/2023 6:14:37 PM
Last indexation05/05/2024 3:32:01 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack