bims-ciryme 2019-09-22 papers

Issue of 2019‒09‒22
two papers selected by
Gabriela Da Silva Xavier
University of Birmingham

Nature. 2019 Sep 18.

Light-entrained and brain-tuned circadian circuits regulate ILC3s and gut homeostasis.

Cristina Godinho-Silva, Rita G Domingues, Miguel Rendas, Bruno Raposo, Hélder Ribeiro, Joaquim Alves da Silva, Ana Vieira, Rui M Costa, Nuno L Barbosa-Morais, Tânia Carvalho, Henrique Veiga-Fernandes.

Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism1. ILC3s and neuronal cells have been shown to interact at discrete mucosal locations to steer mucosal defence2,3. Nevertheless, it is unclear whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3s, intestinal homeostasis, gut defence and host lipid metabolism in mice. We found that enteric ILC3s display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, a deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut 'postcode receptors' of ILC3s. Strikingly, light-dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals being the major entraining cues of ILC3s. Accordingly, surgically or genetically induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, a deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3s, shaping intestinal health, metabolism and organismal homeostasis.

DOI: https://doi.org/10.1038/s41586-019-1579-3

Comp Med. 2019 Sep 20.

Influence of Daytime LED Light Exposure on Circadian Regulatory Dynamics of Metabolism and Physiology in Mice.

Robert T Dauchy, David E Blask, Aaron E Hoffman, Shulin Xiang, John P Hanifin, Benjamin Warfield, George C Brainard, Murali Anbalagan, Lynell M Dupepe, Georgina L Dobek, Victoria P Belancio, Erin M Dauchy, Steven M Hill.

Light is a potent biologic force that profoundly influences circadian, neuroendocrine, and neurobehavioral regulation inanimals. Previously we examined the effects of light-phase exposure of rats to white light-emitting diodes (LED), which emit more light in the blue-appearing portion of the visible spectrum (465 to 485 nm) than do broad-spectrum cool white fluorescent (CWF) light, on the nighttime melatonin amplitude and circadian regulation of metabolism and physiology. In the current studies, we tested the hypothesis that exposure to blue-enriched LED light at day (bLAD), compared withCWF, promotes the circadian regulation of neuroendocrine, metabolic, and physiologic parameters that are associated with optimizing homeostatic regulation of health and wellbeing in 3 mouse strains commonly used in biomedical research (C3H [melatonin-producing], C57BL/6, and BALB/c [melatonin-non-producing]). Compared with male and female mice housed for 12 wk under 12:12-h light:dark (LD) cycles in CWF light, C3H mice in bLAD evinced 6-fold higher peak plasma melatonin levels at the middark phase; in addition, high melatonin levels were prolonged 2 to 3 h into the light phase. C57BL/6 andBALB/c strains did not produce nighttime pineal melatonin. Body growth rates; dietary and water intakes; circadian rhythmsof arterial blood corticosterone, insulin, leptin, glucose, and lactic acid; pO2 and pCO2; fatty acids; and metabolic indicators(cAMP, DNA, tissue DNA 3H-thymidine incorporation, fat content) in major organ systems were significantly lower and activation of major metabolic signaling pathways (mTOR, GSK3β, and SIRT1) in skeletal muscle and liver were higher only in C3H mice in bLAD compared with CWF. These data show that exposure of C3H mice to bLAD compared with CWF has a marked positive effect on the circadian regulation of neuroendocrine, metabolic, and physiologic parameters associatedwith the promotion of animal health and wellbeing that may influence scientific outcomes. The absence of enhancement in amelatonic strains suggests hyperproduction of nighttime melatonin may be a key component of the physiology.

DOI: https://doi.org/10.30802/AALAS-CM-19-000001