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In this context, the higher inflammatory readouts at ZT12 may represent a normal time-of-day-dependent oscillatory state rather than a purely pathological increase.Citation 51 From this perspective, the key pathological effect of HFD is not simply that it elevates inflammatory markers, but that it disrupts their normal temporal organization, resulting in persistently elevated and arrhythmic inflammatory tone.Citation 52 This finding prompted a higher-resolution temporal analysis across six time points, which confirmed that HFD severely disrupted circadian rhythmicity,Citation 53 markedly dampening the amplitude of diurnal oscillations in key mediators, including Tnf , Il6 , Ccl2 , and Nos2 .Citation 54 , Citation 55 This disruption led to persistently elevated inflammatory tone throughout the 24-hour cycle.Citation 56 Intervention with FOS effectively restored these rhythmic patterns via microbiota-dependent mechanisms, as antibiotic treatment completely abolished the effect