Integrated transcriptomic and metabolomic analysis reveals adaptive changes of hibernating retinas

Abstract

Hibernation is a seasonally adaptive strategy that allows hibernators to live through extremely cold conditions. Despite the profound reduction of blood flow to the retinas, hibernation causes no lasting retinal injury. Instead, hibernators show an increased tolerance to ischemic insults during the hibernation period. To understand the molecular changes of the retinas in response to hibernation, we applied an integrative transcriptome and metabolome analysis to explore changes in gene expression and metabolites of 13-lined ground squirrel retinas during hibernation. Metabolomic analysis showed a global decrease of ATP synthesis in hibernating retinas. Decreased glucose and galactose, increased beta-oxidation of carnitine and decreased storage of some amino acids in hibernating retinas indicated a shift of fuel use from carbohydrates to lipids and alternative usage of amino acids. Transcriptomic analysis revealed that the down-regulated genes were enriched in DNA-templated transcription and immune-related functions, while the up-regulated genes were enriched in mitochondrial inner membrane and DNA packaging-related functions. We further showed that a subset of genes underwent active alternative splicing events in response to hibernation. Finally, integrative analysis of the transcriptome and metabolome confirmed the shift of fuel use in the hibernating retina by the regulation of catabolism of amino acids and lipids. Through transcriptomic and metabolomic data, our analysis revealed the altered state of mitochondrial oxidative phosphorylation and the shift of energy source in the hibernating retina, advancing our understanding of the molecular mechanisms employed by hibernators. The data will also serve as a useful resource for the ocular and hibernation research communities.

Gene expression profiling during hibernation in the European hamster

“…Therefore, the increased central MT 2 expression observed upon arousal indicates that this receptor may be involved in the neuroprotective function of melatonin during hibernation. This function may be particularly relevant in the retina, which expresses high levels of MT 2 and displays profound synaptic remodelling during hibernation 62–64 . Melatonin also reportedly activates arousal thermogenesis through peripheral actions 65–68 ; however, our data did not reveal significant changes in MT 1 expressions in any peripheral organs and a decrease of MT2 in the BAT.…”

Engineering Human Stasis for Long-Duration Spaceflight

“…This and other metabolomics data sets underscore a pattern whereby arousals restore levels of metabolites that either deplete or accumulate during torpor (34). Metabolomic, pro-teomic and transcriptome data sets highlight a shift away from glucose toward fatty acids as the primary fuel during hibernation (3,44,45,73,81,82,97,115), which may itself be protective against ischemia-reperfusion damage (13). Elevated betahydroxybutyrate, typical of hibernation, is also protective in a hemorrhagic shock model (87).…”

Regulatory metabolism over the hibernation‐activity cycle changes contribute to the adaptive enhancement of leech ( Whitmania pigra )

“…In hibernation, mitochondrial metabolic suppressed, and respiration was inhibited between succinate dehydrogenase and cytochrome c oxidase (Chung et al., 2011; Muleme et al., 2006). Decreases in galactose and glucose decreased and beta‐oxidation of fatty acids increased in hibernators, supporting hibernator switches from carbohydrate to enhanced lipids metabolism, the level of fatty acids increased during hibernation (Luan et al., 2018). Polyunsaturated fatty acids can result in enhanced energy savings during hibernation (Giroud et al., 2019), and n‐3 polyunsaturated fatty acids could control carbohydrate metabolism (Chazarin et al., 2019).…”