Acute heat stress reprograms the circadian-inflammatory-metabolic axis in Lasiopodomys brandtii.

Ongoing climate warming, particularly intensifying heatwaves, imposes substantial physiological stress on small mammals. Although heat-induced responses have been extensively studied in laboratory models, little is known about how wild small mammals respond to acute thermal stress. To address this gap, we investigated the physiological responses of Brandt's voles (Lasiopodomys brandtii), a diurnal herbivorous rodent native to typical steppe regions of Inner Mongolia, under acute heat exposure (36 °C). Heat-treated voles showed a 1.4 °C rise in core body temperature and a 37 % reduction in metabolic rate, accompanied by a phase advance in the circadian rhythm and the emergence of an 11.8 h ultradian rhythm. Gene expression profiling revealed upregulation of circadian repressors (Per2 and Cry1) and pro-inflammatory genes (Nfκb or Il1α) in the hypothalamus, liver and brown adipose tissue (BAT), and tissue-specific alterations in thermogenic regulators (Pgc1α). Concurrent with these changes, serum TNF-α levels elevated, IL-6 reduced, and thyroxine (T4) increased, while serum T3 remained stable. Correlation analyses showed that Per2 and Cry1 expression in the liver, but not in the hypothalamus or BAT, were positively associated with serum TNF-α, whereas in the hypothalamus and BAT, clock genes were primarily linked to local inflammatory markers such as Nfκb and Il1α. Network modeling further identified Per2 and Bmal1 as central hub genes across tissues, orchestrating regulatory interactions with both inflammatory and metabolic genes. These findings suggest that heat-induced circadian disruption involves tissue-specific interactions between clock genes and immune-metabolic signals, underscoring the circadian system's key role in coordinating adaptive responses to acute thermal stress.