Mechanisms of energy metabolism reprogramming and homeostasis maintenance in overwintering hibernating animals.

Hibernation is a specialized adaptive energy-saving survival strategy evolved by animals to withstand winter cold stress and food scarcity. Its core feature lies in profound metabolic suppression, characterized by a drastic reduction in metabolic rate during hibernation, accompanied by the coordinated downregulation of multiple physiological functions such as body temperature, heart rate, and respiratory rate. The establishment and maintenance of this deep metabolic suppression state essentially rely on the systemic reprogramming of energy metabolism, which serves as the core driving force of hibernation adaptation. During this reprogramming process, lipid metabolism acts as a key executive link: fats stored in adipose tissue not only function as the primary energy reserve pool during hibernation but also undergo precise regulatory remodeling in terms of their compositional characteristics, mobilization efficiency, and catabolic processes, thereby synchronously adapting to the demands of energy supply and environmental adaptation goals. Importantly, metabolic suppression often precedes cooling and can exceed Q10 predictions, indicating active regulatory control rather than passive thermal effects. Reliance on lipid oxidation and cyclic torpor-arousal transitions should heighten oxidative stress risk: electron leakage from mitochondrial complexes I/III during deep torpor, relative hypoxia from reduced perfusion, and rapid "metabolic restart" upon arousal may resemble ischemia-reperfusion. Yet hibernators show minimal oxidative damage, implying robust antioxidant and repair programs. This review summarizes recent advances in the metabolic remodeling of lipids, substrate conversion, and oxidative stress adaptation in hibernating animals. It reveals the evolutionary mechanisms underlying energy metabolism adaptation and provides potential insights for applications in metabolic diseases, cryobiology, and related fields.