Shifting eating to the circadian rest phase misaligns the peripheral clocks with the master SCN clock and leads to a metabolic syndrome.
The light-entrained master central circadian clock (CC) located in the suprachiasmatic nucleus (SCN) not only controls the diurnal alternance of the active phase (the light period of the human light-dark cycle, but the mouse dark period) and the rest phase (the human dark period, but the mouse light period), but also synchronizes the ubiquitous peripheral CCs (PCCs) with these phases to maintain homeostasis. We recently elucidated in mice the molecular signals through which metabolic alterations induced on an unusual feeding schedule, taking place during the rest phase [i.e., restricted feeding (RF)], creates a 12-h PCC shift. Importantly, a previous study showed that the SCN CC is unaltered during RF, which creates a misalignment between the RF-shifted PCCs and the SCN CC-controlled phases of activity and rest. However, the molecular basis of SCN CC insensitivity to RF and its possible pathological consequences are mostly unknown. Here we deciphered, at the molecular level, how RF creates this misalignment. We demonstrate that the PPARα and glucagon receptors, the two instrumental transducers in the RF-induced shift of PCCs, are not expressed in the SCN, thereby preventing on RF a shift of the master SCN CC and creating the misalignment. Most importantly, this RF-induced misalignment leads to a misexpression (with respect to their normal physiological phase of expression) of numerous CC-controlled homeostatic genes, which in the long term generates in RF mice a number of metabolic pathologies including diabetes, obesity, and metabolic syndrome, which have been reported in humans engaged in shift work schedules.
['Mukherji|Atish|A|', 'Kobiita|Ahmad|A|', 'Damara|Manohar|M|', 'Misra|Nisha|N|', 'Meziane|Hamid|H|', 'Champy|Marie-France|MF|', 'Chambon|Pierre|P|']
D000818:Animals D057906:Circadian Clocks D002940:Circadian Rhythm D003920:Diabetes Mellitus D004195:Disease Models, Animal D004435:Eating D005247:Feeding Behavior D005786:Gene Expression Regulation D038362:Glycogen Synthase Kinase 3 D000071679:Glycogen Synthase Kinase 3 beta D006937:Hypercholesterolemia D015228:Hypertriglyceridemia D008099:Liver D008297:Male D024821:Metabolic Syndrome D051379:Mice D008810:Mice, Inbred C57BL D056950:Period Circadian Proteins D010766:Phosphorylation D017440:Photoperiod D051780:Sterol Regulatory Element Binding Protein 1 D013493:Suprachiasmatic Nucleus D013997:Time Factors D014940:Work Schedule Tolerance
metabolic syndrome mouse diabetes shift work circadian clocks misalignment