bims-ciryme 2019-05-26 papers

Issue of 2019‒05‒26
two papers selected by
Gabriela Da Silva Xavier
University of Birmingham

Cell Rep. 2019 May 21. pii: S2211-1247(19)30573-X. [Epub ahead of print]27(8): 2385-2398.e3

Light Entrains Diurnal Changes in Insulin Sensitivity of Skeletal Muscle via Ventromedial Hypothalamic Neurons.

Ebru Aras, Giorgio Ramadori, Kenichiro Kinouchi, Yu Liu, Rafael M Ioris, Xavier Brenachot, Sanda Ljubicic, Christelle Veyrat-Durebex, Silvia Mannucci, Mirco Galié, Pierre Baldi, Paolo Sassone-Corsi, Roberto Coppari.

Loss of synchrony between geophysical time and insulin action predisposes to metabolic diseases. Yet the brain and peripheral pathways linking proper insulin effect to diurnal changes in light-dark and feeding-fasting inputs are poorly understood. Here, we show that the insulin sensitivity of several metabolically relevant tissues fluctuates during the 24 h period. For example, in mice, the insulin sensitivity of skeletal muscle, liver, and adipose tissue is lowest during the light period. Mechanistically, by performing loss- and gain-of-light-action and food-restriction experiments, we demonstrate that SIRT1 in steroidogenic factor 1 (SF1) neurons of the ventromedial hypothalamic nucleus (VMH) convey photic inputs to entrain the biochemical and metabolic action of insulin in skeletal muscle. These findings uncover a critical light-SF1-neuron-skeletal-muscle axis that acts to finely tune diurnal changes in insulin sensitivity and reveal a light regulatory mechanism of skeletal muscle function.

DOI: https://doi.org/10.1016/j.celrep.2019.04.093

EMBO J. 2019 May 24. pii: e101347. [Epub ahead of print]

Nutrient-sensitive transcription factors TFEB and TFE3 couple autophagy and metabolism to the peripheral clock.

Nunzia Pastore, Anna Vainshtein, Niculin J Herz, Tuong Huynh, Lorenzo Brunetti, Tiemo J Klisch, Margherita Mutarelli, Patrizia Annunziata, Kenichiro Kinouchi, Nicola Brunetti-Pierri, Paolo Sassone-Corsi, Andrea Ballabio.

Autophagy and energy metabolism are known to follow a circadian pattern. However, it is unclear whether autophagy and the circadian clock are coordinated by common control mechanisms. Here, we show that the oscillation of autophagy genes is dependent on the nutrient-sensitive activation of TFEB and TFE3, key regulators of autophagy, lysosomal biogenesis, and cell homeostasis. TFEB and TFE3 display a circadian activation over the 24-h cycle and are responsible for the rhythmic induction of genes involved in autophagy during the light phase. Genetic ablation of TFEB and TFE3 in mice results in deregulated autophagy over the diurnal cycle and altered gene expression causing abnormal circadian wheel-running behavior. In addition, TFEB and TFE3 directly regulate the expression of Rev-erbα (Nr1d1), a transcriptional repressor component of the core clock machinery also involved in the regulation of whole-body metabolism and autophagy. Comparative analysis of the cistromes of TFEB/TFE3 and REV-ERBα showed an extensive overlap of their binding sites, particularly in genes involved in autophagy and metabolic functions. These data reveal a direct link between nutrient and clock-dependent regulation of gene expression shedding a new light on the crosstalk between autophagy, metabolism, and circadian cycles.

Keywords: MiT‐TFE; REV‐ERBα; circadian rhythm; gene oscillation

DOI: https://doi.org/10.15252/embj.2018101347