bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2020‒03‒29
two papers selected by
Gabriela Da Silva Xavier
University of Birmingham

  1. FASEB J. 2020 Mar 24.
      Circadian clock confers temporal control in metabolism, with its disruption leading to the development of insulin resistance. Metabolic substrate utilization in skeletal muscle is coordinated with diurnal nutrient cycles. However, whether the molecular clock is involved in this coordination is largely unknown. Using a myocyte-selective genetic ablation mouse model of the essential clock activator Bmal1, here we identify muscle-intrinsic clock as a sensor of feeding cues to orchestrate skeletal muscle oxidation required for global nutrient flux. Bmal1 in skeletal muscle responds robustly to feeding in vivo and insulin induces its expression. Muscle Bmal1 deficiency impaired the transcriptional control of glucose metabolic pathway, resulting in markedly attenuated glucose utilization and fasting hyperglycemia. Notably, the loss of Bmal1 response to feeding abolished fasting-to-feeding metabolic fuel switch from fatty acids to glucose in skeletal muscle, leading to the activation of energy-sensing pathways for fatty acid oxidation. These altered metabolic substrate oxidations in Bmal1-deficient muscle ultimately depleted circulating lipid levels that prevented hepatic steatosis. Collectively, our findings highlight the key role of the metabolic-sensing function of skeletal muscle clock in partitioning nutrient flux between muscle and liver to maintain whole-body lipid and glucose homeostasis.
    Keywords:  circadian clock; fatty acid metabolism; glucose metabolism; hepatic steatosis; skeletal muscle
  2. Acta Biotheor. 2020 Mar 25.
      In the 1960's Brian Goodwin published a couple of mathematical models showing how feedback inhibition can lead to oscillations and discussed possible implications of this behaviour for the physiology of the cell. He also presented key ideas about the rich dynamics that may result from the coupling between such biochemical oscillators. Goodwin's work motivated a series of theoretical investigations aiming at identifying minimal mechanisms to generate limit cycle oscillations and deciphering design principles of biological oscillators. The three-variable Goodwin model (adapted by Griffith) can be seen as a core model for a large class of biological systems, ranging from ultradian to circadian clocks. We summarize here main ideas and results brought by Goodwin and review a couple of modeling works directly or indirectly inspired by Goodwin's findings.
    Keywords:  Circadian rhythms; Feedback inhibition; Goodwin model; Limit cycle oscillations