Abstract
Epidemiological studies indicate that shift-workers have an increased risk of type 2 diabetes mellitus (T2DM). Glucose tolerance and insulin sensitivity both are dependent on the circadian timing system (i.e., the time-of-day) and fasting duration, in rodents as well as humans. Therefore, question is whether manipulation of the circadian timing system, for example by changing the timing of feeding and fasting, is a potential preventive treatment for T2DM. Time-restricted feeding (TRF) is well-known to have profound effects on various metabolic measures, including glucose metabolism. However, experiments that directly measure the effects of TRF on glucose tolerance and/or insulin sensitivity at different time points throughout the 24 h cycle are lacking. Here we show, in rats, that TRF in line with the circadian timing system (i.e., feeding during the active phase) improves glucose tolerance during intravenous glucose tolerance tests (ivGTT) in the active phase, as lower insulin levels were observed with similar levels of glucose clearance. However, this was not the case during the inactive phase in which more insulin was released but only a slightly faster glucose clearance was observed. Contrasting, TRF out of sync with the circadian timing system (i.e., feeding during the inactive phase) worsened glucose tolerance, although only marginally, likely because of adaptation to the 4 week TRF regimen. Our results show that TRF can improve glucose metabolism, but strict adherence to the time-restricted feeding period is necessary, as outside the regular eating hours glucose tolerance is worsened.
Highlights
An increasing number of people are suffering from type 2 diabetes mellitus (T2DM) [1]
Glucose Responses For all three groups in the time-restricted feeding (TRF) experiment, the intravenously administered glucose was cleared from the circulation within 20 min at both ZT4 and ZT16, i.e., blood glucose levels had returned to baseline or were even slightly lower than baseline (Figures 2A,B)
In case the daily variation in glucose tolerance would have been completely dependent on the prior feeding/fasting condition, it would be expected that the daily variation in glucose and insulin responses in dark fed animals would be comparable to those of ad libitum animals, whereas those of light fed animals would be the reverse (i.e., 12 h shifted)
Summary
An increasing number of people are suffering from type 2 diabetes mellitus (T2DM) [1]. A widely used animal model to study the metabolic effects of shift-work is time-restricted feeding (TRF) in which the opportunity to eat, but not the amount, is restricted to a certain period of the day [reviewed in [4, 5]] In nocturnal animals such as mice and rats the chosen period is usually (part of) the light period (=inactive phase) to mimic shift work and (part of) the dark period (=active phase) as a control condition. Glucose tolerance tests (GTT) to study the effects of TRF on glucose metabolism are usually only performed at one time point [7,8,9,10] It is not clear how much of the variation found is due to (changes in) the circadian timing system [11] or to differences in the preceding fasting period. As TRF during the active phase is associated with metabolic health improvements and TRF during the inactive phase with negative health effects we hypothesized that animals fed only during the dark/active period would show improved glucose tolerance, whilst animals only fed during the light/inactive period would show impaired glucose tolerance
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