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During winter hibernation in mammals, body temperature falls to near‐ambient levels, metabolism shifts to favor lipid oxidation, and metabolic rate is strongly suppressed by inhibiting many ATP‐expensive processes (e.g., transcription, translation) for animals in order to survive for many months on limited reserves of body fuels. Regulation of such profound changes (i.e., metabolic rate depression) requires rapid and reversible controls provided by protein posttranslational modifications. Protein lysine methylation provides one mechanism by which the functionality, activity, and stability of cellular proteins and enzymes can be modified for the needs of the hibernator. The present study reports the responses of seven lysine methyltransferases (SMYD2, SUV39H1, SET8, SET7/9, G9a, ASH2L, and RBBP5) in skeletal muscle and liver over seven stages of the torpor/arousal cycle in 13‐lined ground squirrels (Ictidomys tridecemlineatus). A tissue‐specific and stage‐specific analysis revealed significant changes in the protein levels of lysine methyltransferases, methylation patterns on histone H3, histone methyltransferase activity, and methylation of the p53 transcription factor. Enzymes typically increased in protein amount in either torpor, arousal, or the transitory periods. Methylation of histone H3 and p53 typically followed the patterns of the methyltransferase enzymes. Overall, these data show that protein lysine methylation is an important regulator of the mammalian hibernation phenotype.

The fatty acid composition of a pre-hibernation diet can influence the depth and duration of metabolic suppression achieved by hibernators. More specifically, a diet high in n−6 polyunsaturated fatty acids (PUFAs) relative to n−3 PUFAs is essential to maximize torpor expression. However, few studies have investigated how diets with different n−6/n−3 PUFA ratios change stress-inducible cell signaling. Garden dormice (Eliomys quercinus) were fed one of three diets designed with different ratios of n−6 PUFA linoleic acid (LA) and n−3 PUFA linolenic acid (ALA). Then, NFκB signaling was assessed in the white adipose, brown adipose, and liver tissues of euthermic and hibernating dormice via multiplex and RT-qPCR analyses of relative protein and transcript levels, respectively. Dormice fed a high LA diet regulated NFκB signaling in a protective manner in all tissues. NFκB signaling was generally decreased in the high LA group, with significant decreases in the protein levels of NFκB mediators IKKα/β, IκBα, and downstream pro-apoptotic protein FADD. Liver and white adipose from torpid dormice fed a high LA diet increased sod2 expression relative to the other diets or relative to euthermic controls, indicating protection against ROS generated from potentially increased β-oxidation of n−6 PUFAs. The low LA diet increased biomarkers for apoptosis relative to other diets and relative to euthermia, suggesting low LA diets may be detrimental to hibernator health. Overall, this study suggests that changes in the ratio of n−6/ n−3 PUFAs in the diet influences apoptotic and antioxidant responses in white adipose, brown adipose, and liver of hibernating garden dormice.