Natural food intake patterns have little synchronizing effect on peripheral circadian clocks

BMC Biology

Joseph P. Garner¹  Alec M. Berman²  Ayaka Kukino²  Haley E. Calcagno²  Xiaobin Xie³  Matthew P. Butler⁴ 

[1]Department of Comparative Medicine, Stanford University, Stanford, CA, USA

[2]Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, 3181 SW Sam Jackson Park Road – L606, 97239, Portland, OR, USA

[3]Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, 3181 SW Sam Jackson Park Road – L606, 97239, Portland, OR, USA

[4]Current Address: Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, 511436, Guangzhou, China

[5]Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, 3181 SW Sam Jackson Park Road – L606, 97239, Portland, OR, USA

[6]Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA

关键词: Meal timing;    Peripheral clocks;    Liver;    Kidney;    TRF;    Time-restricted feeding;    Period circadian proteins;    Activity cycles;    Constant darkness;   

DOI  :  10.1186/s12915-020-00872-7

来源: Springer

【 摘 要 】

BackgroundCircadian rhythms across mammalian tissues are coordinated by a master clock in the suprachiasmatic nucleus (SCN) that is principally entrained by light-dark cycles. Prior investigations have shown, however, that time-restricted feeding (TRF)—daily alternation of fasting and food availability—synchronizes peripheral clocks independent of the light-dark cycle and of the SCN. This has led to the idea that downstream peripheral clocks are entrained indirectly by food intake rhythms. However, TRF is not a normal eating pattern, and it imposes non-physiologic long fasts that rodents do not typically experience. Therefore, we tested whether normal feeding patterns can phase-shift or entrain peripheral tissues by measuring circadian rhythms of the liver, kidney, and submandibular gland in mPer2Luc mice under different food schedules.ResultsWe employed home cage feeders to first measure ad libitum food intake and then to dispense 20-mg pellets on a schedule mimicking that pattern. In both conditions, PER2::LUC bioluminescence peaked during the night as expected. Surprisingly, shifting the scheduled feeding by 12 h advanced peripheral clocks by only 0–3 h, much less than predicted from TRF protocols. To isolate the effects of feeding from the light-dark cycle, clock phase was then measured in mice acclimated to scheduled feeding over the course of 3 months in constant darkness. In these conditions, peripheral clock phases were better predicted by the rest-activity cycle than by the food schedule, contrary to expectation based on TRF studies. At the end of both experiments, mice were exposed to a modified TRF with food provided in eight equally sized meals over 12 h. In the light-dark cycle, this advanced the phase of the liver and kidney, though less so than in TRF with ad libitum access; in darkness, this entrained the liver and kidney but had little effect on the submandibular gland or the rest-activity cycle.ConclusionsThese data suggest that natural feeding patterns can only weakly affect circadian clocks. Instead, in normally feeding mice, the central pacemaker in the brain may set the phase of peripheral organs via pathways that are independent of feeding behavior.

【 授权许可】

CC BY