bims-ciryme 2021-01-10 papers

Epilepsia. 2021 Jan 04.

Molecular regulation of brain metabolism underlying circadian epilepsy.

Extensive study has demonstrated that epilepsy occurs with greater frequency at certain times in the 24-h cycle. Although these findings implicate an overlap between the circadian rhythm and epilepsy, the molecular and cellular mechanisms underlying this circadian regulation are poorly understood. Because the 24-h rhythm is generated by the circadian molecular system, it is not surprising that this system comprised of many circadian genes is implicated in epilepsy. We summarized evidence in the literature implicating various circadian genes such as Clock, Bmal1, Per1, Rev-erb⍺, and Ror⍺ in epilepsy. In various animal models of epilepsy, the circadian oscillation and the steady-state level of these genes are disrupted. The downstream pathway of these genes involves a large number of metabolic pathways associated with epilepsy. These pathways include pyridoxal metabolism, the mammalian target of rapamycin pathway, and the regulation of redox state. We propose that disruption of these metabolic pathways could mediate the circadian regulation of epilepsy. A greater understanding of the cellular and molecular mechanism of circadian regulation of epilepsy would enable us to precisely target the circadian disruption in epilepsy for a novel therapeutic approach.

Keywords: circadian; clock genes; epigenetic; epilepsy; metabolism

DOI: https://doi.org/10.1111/epi.16796

Function (Oxf). 2021 ;2(1): zqaa034

Timing of Food Intake Drives the Circadian Rhythm of Blood Pressure.

Dingguo Zhang, Jackson C Colson, Chunhua Jin, Bryan K Becker, Megan K Rhoads, Paramita Pati, Thomas H Neder, McKenzi A King, Jennifer A Valcin, Binli Tao, Malgorzata Kasztan, Jodi R Paul, Shannon M Bailey, Jennifer S Pollock, Karen L Gamble, David M Pollock.

Timing of food intake has become a critical factor in determining overall cardiometabolic health. We hypothesized that timing of food intake entrains circadian rhythms of blood pressure (BP) and renal excretion in mice. Male C57BL/6J mice were fed ad libitum or reverse feeding (RF) where food was available at all times of day or only available during the 12-h lights-on period, respectively. Mice eating ad libitum had a significantly higher mean arterial pressure (MAP) during lights-off compared to lights-on (113 ± 2 mmHg vs 100 ± 2 mmHg, respectively; P < 0.0001); however, RF for 6 days inverted the diurnal rhythm of MAP (99 ± 3 vs 110 ± 3 mmHg, respectively; P < 0.0001). In contrast to MAP, diurnal rhythms of urine volume and sodium excretion remained intact after RF. Male Bmal1 knockout mice (Bmal1KO) underwent the same feeding protocol. As previously reported, Bmal1KO mice did not exhibit a diurnal MAP rhythm during ad libitum feeding (95 ± 1 mmHg vs 92 ± 3 mmHg, lights-off vs lights-on; P > 0.05); however, RF induced a diurnal rhythm of MAP (79 ± 3 mmHg vs 95 ± 2 mmHg, lights-off vs lights-on phase; P < 0.01). Transgenic PERIOD2::LUCIFERASE knock-in mice were used to assess the rhythm of the clock protein PERIOD2 in ex vivo tissue cultures. The timing of the PER2::LUC rhythm in the renal cortex and suprachiasmatic nucleus was not affected by RF; however, RF induced significant phase shifts in the liver, renal inner medulla, and adrenal gland. In conclusion, the timing of food intake controls BP rhythms in mice independent of Bmal1, urine volume, or sodium excretion.

Keywords: Bmal1; blood pressure; circadian rhythms; sodium excretion; time-restricted feeding

DOI: https://doi.org/10.1093/function/zqaa034

J Clin Invest. 2021 Jan 04. pii: 144655. [Epub ahead of print]131(1):

You are when you eat: on circadian timing and energy balance.

Jonathan Cedernaes, Joseph Bass.

The neuronal mechanisms that establish 24-hour rhythms in feeding and metabolism remain incompletely understood. In this issue of the JCI, Adlanmerini and colleagues explored the relationship between temporal and homeostatic control of energy balance by focusing on mice that lacked the genes encoding the clock repressor elements REV-ERBα and -β, specifically in the tuberal hypothalamus. Notably, the clock transcription cycle mediated intraneuronal response to the adipostatic hormone leptin. These results show that REV-ERBα and -β in the hypothalamus are necessary for maintaining leptin responsiveness and metabolic homeostasis and lay the foundation to explore how transcriptional changes may link energy-sensing cell types with day/night rhythms. Such information may lead to therapeutics that alleviate the adverse effects of chronic shift work.

DOI: https://doi.org/10.1172/JCI144655