Sleep disorders are prevalent in chronic kidney disease patients, although the underlying mechanisms are not understood. The current study demonstrates that adenine-induced tubulointerstitial nephropathy disrupted the circadian system both centrally and in peripheral organs. Clock mutant mice were also more vulnerable to the effects of adenine. These findings aid the understanding of sleep disturbances in adenine phosphoribosyltransferase deficiency, a rare inherited metabolic disorder that leads to the accumulation of 2,8dihydroxyadenine. More broadly, the results suggest that circadian disruption caused by environmental factors such as nighttime shift work may be a risk factor for chronic kidney disease development.

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Highlights d Distribution of dietary protein across meals influences muscle hypertrophy d BCAAs are involved in hypertrophic effects of protein feeding distribution d Hypertrophic effects of protein feeding distribution require the muscle clock d Breakfast protein intake is correlated with skeletal muscle functions in older women

BackgroundAtrogin1, which is one of the key genes for the promotion of muscle atrophy, exhibits day-night variation. However, its mechanism and the role of its day-night variation are largely unknown in a muscle atrophic context.MethodsThe mice were induced a muscle atrophy by hindlimb-unloading (HU). To examine a role of circadian clock, Wild-type (WT) and Clock mutant mice were used. To test the effects of a neuronal effects, an unilateral ablation of sciatic nerve was performed in HU mice. To test a timing-dependent effects of weight-bearing, mice were released from HU for 4 h in a day at early or late active phase (W-EAP and W-LAP groups, respectively).FindingsWe found that the day-night oscillation of Atrogin1 expression was not observed in Clock mutant mice or in the sciatic denervated muscle. In addition, the therapeutic effects of weight-bearing were dependent on its timing with a better effect in the early active phase.InterpretationThese findings suggest that the circadian clock controls the day-night oscillation of Atrogin1 expression and the therapeutic effects of weight-bearing are dependent on its timing.FundCouncil for Science, Technology, and Innovation, SIP, “Technologies for creating next-generation agriculture, forestry, and fisheries”.

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