Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks (2018). Cell 174: 1571-1585

Dyar, Lutter, Artati, Ceglia, Liu, Armenta, Jastroch, Schneider, de Mateo, Cervantes, Abbondate, Tognini, Orozco-Solis, Kinouchi, Wang, Swedloff, Nadeef, Masri, Magistretti, Orlando, Borrelli, Uhlenhaut, Baldi, Adamski, Tschop, Eckel-Mahan, and Sassone-Corsi

Metabolic diseases are often characterized by circadian misalignment in different tissues, yet how altered coordination and communication among tissue clocks relate to specific pathogenic mechanisms remains largely unknown. Applying an integrated systems biology approach, we performed 24-hr metabolomics profiling of eight mouse tissues simultaneously.

Defining the Independence of the Liver Circadian Clock (2019). Cell 177: 1448-1462

Koronowski, Kinouchi, Welz, Smith, Zinnam Shi, Samad, Chen, Magnan, Kinchen, Li, Baldi, Benitah, and Sassone-Corsi

An autonomous branch of the liver circadian clock is independent from all other clocks yet still dependent on the light-dark cycle.

BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis (2019). Cell 177: 1436-1447

Well, Inna, Symeonidi, Koronowski, Kinouchi, Smith, Guillén, Castellanos, Crainicius, Prats, Caballero, Hidalgo, Sassone-Corsi, and Benitah

We show that unexpectedly, light synchronizes the Bmal1-dependent circadian machinery in single tissues in the absence of Bmal1 in all other tissues. Strikingly, light-driven tissue autonomous clocks occur without rhythmic feeding behavior and are lost in constant darkness. Importantly, tissue-autonomous Bmal1 partially sustains homeostasis in otherwise arrhythmic and prematurely aging animals.

Nutrient-Sensitive Transcription Factors TFFEB and TFE3 Couple Autophagy and Metabolism to the Peripheral Clock (2019). EMBO J 38

Pastore, Vainshtein, Herz, Huynh, Brunetti, Klisch, Mutarelli, Annunziata, Kinouchi, Brunetti-Pierri, Sassone-Corsi, and 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. 

Light Entrains Diurnal Changes in Insulin Sensitivity of Skeletal Muscle Via Ventromedial Hypothalamic Neurons (2019). Cell Reports 27: 2385-2398

Aras, Ramadori, Kinouchi, Liu, Loris, Brenachot, Ljubicic, Veyrat-Durebex, Mannucci, Gailé, Balid, Sassone-Corsi, and 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 hour period.

Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis (2019). Cell Metabolism 30: 92-110

Distinct response of metabolic cycles in skeletal muscle to time-of-day exercise. Early active phase exercise exerts a robust metabolic response in skeletal muscle. The metabolic response includes glycolysis, lipid oxidation, and BCAA breakdown. Time of exercise specifies the activation of HIF1α and systemic energy expenditure.

Sato, Basse, Schonke, Chen, Samad, Altintas, Laker, Dalbram, Barres, Baldi, Treebak, Zierath, and Sassone-Corsi

Modification of Histone Proteins by Serotonin in the Nucleus (2019). Nature 567: 464-465

Cervantes and Sassone-Corsi

The function of histone proteins can be modified through addition or removal of certain chemical groups. The addition of a serotonin molecule is a newly found histone modification that could influence gene expression.

Circadian Blueprint of Metabolic Pathways in the Brain (2019). Nature Reviews Neuroscience 20: 71-82

Greco and Sassone-Corsi

The circadian clock is an endogenous, time-tracking system that directs multiple metabolic and physiological functions required for homeostasis. The master or central clock located within the suprachiasmatic nucleus in the hypothalamus governs peripheral clocks present in all systemic tissues, contributing to their alignment and ultimately to temporal coordination of physiology. Accumulating evidence reveals the presence of additional clocks in the brain and suggests the possibility that circadian circuits may feed back to these from the periphery. Here, we highlight recent advances in the communications between clocks and discuss how they relate to circadian physiology and metabolism.

Fasting Imparts a Switch to Alternative Daily Pathways in Liver and Muscle (2018). Cell Reports 25: 3299-3314

Kinouchi, Magnan, Ceglia, Liu, Cervantes, Pastore, Huynh, Ballabio, Baldi, Masri, and Sassone-Corsi

The circadian clock operates as intrinsic time-keeping machinery to preserve homeostasis in response to the changing environment. While food is a known zeitgeber for clocks in peripheral tissues, it remains unclear how lack of food influences clock function. We demonstrate that the transcriptional response to fasting operates through molecular mechanisms that are distinct from time-restricted feeding regimens.

The Emerging Link between Cancer, Metabolism and Circadian Rhythms (2018). Nat Med. 24(12): 1795-1803

Masri and Sassone-Corsi

The circadian clock is a complex cellular mechanism that, through the control of diverse metabolic and gene expression pathways, governs a large array of cyclic physiological processes. Epidemiological and clinical data reveal a connection between the disruption of circadian rhythms and cancer that is supported by recent preclinical data. In addition, the use of animal models and molecular studies indicate emerging links between cancer metabolism and the circadian clock. This has implications for therapeutic approaches and we discuss the possible design of chrono-pharmacological strategies.