Fatty acid metabolization and insulin regulation prevent liver injury from lipid accumulation in Himalayan marmots

Cold resistance of mammalian hibernators ∼ a matter of ferroptosis?

“…Alternatively, the cellular membrane composition of hibernators may be intrinsically distinct from that of non-hibernators, or seasonally adapted to achieve cold resistance and maintain membrane fluidity under cold conditions, which could affect the structure of membrane proteins that are vital for maintaining cellular ion homeostasis ( Aloia and Raison, 1989 ; Giroud et al, 2013 ; Cheff et al, 2021 ). Further efforts to answer these questions in detail will be necessary in specific model hibernators such as Syrian hamsters, in which the causal relationship between genes and phenomena can be functionally addressed, in combination with candidate genes and candidate molecules accumulated through the latest bioinformatics, omics, and comparative approaches in various hibernators, including ground squirrels, marmots, dormice, chipmunks, bats, and bears ( Fedorov et al, 2014 ; Villanueva-Canas et al, 2014 ; Ferris and Gregg, 2019 ; Grabek et al, 2019 ; Jansen et al, 2019 ; Gillen et al, 2021 ; Chen and Mao, 2022 ; Bao et al, 2023 ; Christmas et al, 2023 ; Haugg et al, 2023 ; Heinis et al, 2023 ; Takamatsu et al, 2023 ; Thienel et al, 2023 ; Yang et al, 2023 ). Based on these studies, we will further clarify Q4 and its related question whether cold resistance associated with hibernation originates from a common ancestral trait or as a result of convergent evolution across distinct mammalian clades.…”

The Research Progress on the Interaction between Mammalian Gut Microbiota and the Host’s Metabolism Homeostasis during Hibernation

“…Hibernating species like the 13-lined ground squirrel, Daurian ground squirrel, greater horseshoe bat, and brown bear have undergone thorough studies concerning their gut microbiota [ 2 , 16 , 17 , 18 ]. Due to winter fasting, the host experiences a sharp reduction in degradable substrates available for gut microbiota, which can impact the variety and composition of the gut microbial community [ 19 ].…”

“…However, an overabundance of fat accumulation has the potential to result in liver impairment, manifesting as conditions like non-alcoholic fatty liver disease (NAFLD) [ 47 , 48 ]. Findings from Bao et al indicated that Himalayan marmots in the pre-hibernation active phase exhibit a preference for dietary options abundant in unsaturated fatty acids (UFAs) [ 2 ], and there was a notable positive correlation between the intake of unsaturated fatty acids and body weight [ 49 ]. This preference is potentially attributed to the absence of desaturase enzymes in mammals, which hinders the endogenous synthesis of UFAs.…”

“…This preference is potentially attributed to the absence of desaturase enzymes in mammals, which hinders the endogenous synthesis of UFAs. UFAs are likely instrumental in facilitating the fat accumulation observed in Himalayan marmots [ 2 ]. Metagenomic analysis reveals a significant upregulation in the biosynthesis of UFAs within the Firmicutes CAG:110 .…”

“…During hibernation, animals undergo adaptive changes such as reduced body temperature, slowed metabolism, and decreased heart rate [ 1 ]. The dietary composition of hibernating animals exhibits seasonal variations, with most of them increasing their food intake during the summer and the autumn to store fat, while fasting during hibernation [ 2 , 3 ].…”