Abstract
Daily recurring events can be predicted by animals based on their internal circadian timing system. However, independently from the suprachiasmatic nuclei (SCN), the central pacemaker of the circadian system in mammals, restriction of food access to a particular time of day elicits food anticipatory activity (FAA). This suggests an involvement of other central and/or peripheral clocks as well as metabolic signals in this behavior. One of the metabolic signals that is important for FAA under combined caloric and temporal food restriction is β-hydroxybutyrate (βOHB). Here we show that the monocarboxylate transporter 1 (Mct1), which transports ketone bodies such as βOHB across membranes of various cell types, is involved in FAA. In particular, we show that lack of the Mct1 gene in the liver, but not in neuronal or glial cells, reduces FAA in mice. This is associated with a reduction of βOHB levels in the blood. Our observations suggest an important role of ketone bodies and its transporter Mct1 in FAA under caloric and temporal food restriction.
Highlights
Reproduction, feeding and avoidance of predators are key to survival of animals
Since some monocarboxylate transporters (MCTs, SLC16a family) are responsible for the transport of βOHB, notably through the blood-brain barrier (BBB), we aimed to evaluate the importance of the monocarboxylate transporter 1 (Mct1, Slc16a1) in food anticipation (FA)
Normalization of the activity in the dark phase revealed that Food anticipatory activity (FAA) before ZT4 was reduced compared to controls (Figure 1B, right panel, red), indicating that Mct1 may play a role in the regulation of FAA
Summary
Reproduction, feeding and avoidance of predators are key to survival of animals These three existential processes require precise time-keeping to determine when an animal rests or seeks food. By restricting food to the day or inactivity phase, as in the case of daytime-restricted feeding (RF), mice will adapt and show an increase in activity and internal body temperature before the recurrent food availability (Mistlberger, 2011; Challet, 2019). This adaptation is commonly referred to as food anticipation (FA). This anticipation of feeding time persists for at least 3 days after the food is withdrawn, and it can reappear during food deprivation tests after a week or more of ad libitum feeding
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