Reshaping circadian metabolism in the suprachiasmatic nucleus and prefrontal cortex by nutritional challenge

Food is a powerful entrainment cue for circadian clocks in periph-eral tissues, and changes in the composition of nutrients havebeen demonstrated to metabolically reprogram peripheral clocks.However, how food challenges may influence circadian metabo-lism of the master clock in the suprachiasmatic nucleus (SCN) or inother brain areas is poorly understood. Using high-throughputmetabolomics, we studied the circadian metabolome profiles ofthe SCN and medial prefrontal cortex (mPFC) in lean mice com-pared with mice challenged with a high-fat diet (HFD). Both themPFC and the SCN displayed a robust cyclic metabolism, with astrikingly high sensitivity to HFD perturbation in an area-specificmanner. The phase and amplitude of oscillations were drasticallydifferent between the SCN and mPFC, and the metabolic pathwaysimpacted by HFD were remarkably region-dependent. Further-more, HFD induced a significant increase in the number of cyclingmetabolites exclusively in the SCN, revealing an unsuspected sus-ceptibility of the master clock to food stress.