A Unique Energy-Saving Strategy During Hibernation Revealed by Multi-Omics Analysis in the Chinese Alligator

Overview

Journal iScience

Publisher Cell Press

Date 2020 Jun 14

PMID 32534442

Citations 11

Authors

Jian-Qing Lin

Yun-Yi Huang

Meng-Yao Bian

Qiu-Hong Wan

Sheng-Guo Fang

Affiliations

Soon will be listed here.

Abstract

Many ectotherms hibernate in face of the harsh winter conditions to improve their survival rate. However, the molecular mechanism underlying this process remains unclear. Here, we explored the hibernation mechanism of Chinese alligator using integrative multi-omics analysis. We revealed that (1) the thyroid hormone biosynthesis, nutrition absorption and metabolism, muscle contraction, urinary excretion and immunity function pathways are overall downregulated during hibernation; (2) the fat catabolism is completely suppressed, contrasting with the upregulation of hepatic fatty-acid-transporter CPT1A, suggesting a unique energy-saving strategy that differs from that in hibernating mammals; (3) the hibernation-related genes are not only directly regulated by DNA methylation but also controlled by methylation-dependent transcription networks. In addition, we identified and compared tissue-specific, species-specific, and conserved season-biased miRNAs, demonstrating complex post-transcriptional regulation during hibernation. Our study revealed the genetic and epigenetic mechanisms underlying hibernation in the Chinese alligator and provided molecular insights into the evolution of hibernation regulation.

Citing Articles

The metabolic adaptation in wild vertebrates via omics approaches.

Du X, Hu Y, Huang G, Wei F Life Metab. 2025; 1(3):234-241.

PMID: 39872075 PMC: 11749369. DOI: 10.1093/lifemeta/loac040.

Lipid metabolism and microbial regulation analyses provide insights into the energy-saving strategies of hibernating snakes.

Wei Y, Mao H, Liu Q, Fang W, Zhang T, Xu Y Commun Biol. 2025; 8(1):45.

PMID: 39800781 PMC: 11725596. DOI: 10.1038/s42003-025-07493-2.

Analysis of Lipid Metabolism in Adipose Tissue and Liver of Chinese Soft-Shelled Turtle During Hibernation.

Jin F, You Y, Wan J, Zhu H, Peng K, Hu Z Int J Mol Sci. 2024; 25(22).

PMID: 39596192 PMC: 11595087. DOI: 10.3390/ijms252212124.

Identification of shared gene expression programs activated in multiple modes of torpor across vertebrate clades.

Weir K, Vega N, Busa V, Sajdak B, Kallestad L, Merriman D Sci Rep. 2024; 14(1):24360.

PMID: 39420030 PMC: 11487170. DOI: 10.1038/s41598-024-74324-5.

The Whole Genome DNA Methylation Signatures of Hindlimb Muscles in Chinese Alligators during Hibernation and Active Periods.

Zhang J, Wu X Animals (Basel). 2024; 14(13).

PMID: 38998084 PMC: 11240547. DOI: 10.3390/ani14131972.

References

Zinger L, Bonin A, Alsos I, Balint M, Bik H, Boyer F . DNA metabarcoding-Need for robust experimental designs to draw sound ecological conclusions. Mol Ecol. 2019; 28(8):1857-1862. DOI: 10.1111/mec.15060. View

Su Z, Han L, Zhao Z . Conservation and divergence of DNA methylation in eukaryotes: new insights from single base-resolution DNA methylomes. Epigenetics. 2010; 6(2):134-40. PMC: 3278781. DOI: 10.4161/epi.6.2.13875. View

Lei M, Dong D, Mu S, Pan Y, Zhang S . Comparison of brain transcriptome of the greater horseshoe bats (Rhinolophus ferrumequinum) in active and torpid episodes. PLoS One. 2014; 9(9):e107746. PMC: 4174523. DOI: 10.1371/journal.pone.0107746. View

Inouye D, Barr B, Armitage K, Inouye B . Climate change is affecting altitudinal migrants and hibernating species. Proc Natl Acad Sci U S A. 2000; 97(4):1630-3. PMC: 26486. DOI: 10.1073/pnas.97.4.1630. View

Arfat Y, Chang H, Gao Y . Stress-responsive microRNAs are involved in re-programming of metabolic functions in hibernators. J Cell Physiol. 2017; 233(4):2695-2704. DOI: 10.1002/jcp.26034. View

Krivoruchko A, Storey K . Regulation of the heat shock response under anoxia in the turtle, Trachemys scripta elegans. J Comp Physiol B. 2009; 180(3):403-14. DOI: 10.1007/s00360-009-0414-9. View

Jones P . Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012; 13(7):484-92. DOI: 10.1038/nrg3230. View

Ivascu C, Wasserkort R, Lesche R, Dong J, Stein H, Thiel A . DNA methylation profiling of transcription factor genes in normal lymphocyte development and lymphomas. Int J Biochem Cell Biol. 2007; 39(7-8):1523-38. DOI: 10.1016/j.biocel.2007.02.006. View

Faherty S, Villanueva-Canas J, Blanco M, Alba M, Yoder A . Transcriptomics in the wild: Hibernation physiology in free-ranging dwarf lemurs. Mol Ecol. 2018; 27(3):709-722. DOI: 10.1111/mec.14483. View

10.

Kornfeld S, Biggar K, Storey K . Differential expression of mature microRNAs involved in muscle maintenance of hibernating little brown bats, Myotis lucifugus: a model of muscle atrophy resistance. Genomics Proteomics Bioinformatics. 2012; 10(5):295-301. PMC: 5054200. DOI: 10.1016/j.gpb.2012.09.001. View

11.

Ono M, HOSOE Y, Azuma S, Shoji M, Nara K, Kondo N . HNF-1 regulates the liver-specific transcription of the chipmunk HP-20 gene. Gene. 2001; 277(1-2):121-7. DOI: 10.1016/s0378-1119(01)00699-0. View

12.

Britton C, Mackey D, ESSER V, Foster D, Burns D, Yarnall D . Fine chromosome mapping of the genes for human liver and muscle carnitine palmitoyltransferase I (CPT1A and CPT1B). Genomics. 1997; 40(1):209-11. DOI: 10.1006/geno.1996.4539. View

13.

Fujii G, Nakamura Y, Tsukamoto D, Ito M, Shiba T, Takamatsu N . CpG methylation at the USF-binding site is important for the liver-specific transcription of the chipmunk HP-27 gene. Biochem J. 2006; 395(1):203-9. PMC: 1409699. DOI: 10.1042/BJ20051802. View

14.

Oaks J . A time-calibrated species tree of Crocodylia reveals a recent radiation of the true crocodiles. Evolution. 2011; 65(11):3285-97. DOI: 10.1111/j.1558-5646.2011.01373.x. View

15.

Storey K, Storey J . Molecular biology of freezing tolerance. Compr Physiol. 2013; 3(3):1283-308. DOI: 10.1002/cphy.c130007. View

16.

Xiao Y, Wu Y, Sun K, Wang H, Jiang T, Lin A . Gene expression and adaptive evolution of ZBED1 in the hibernating greater horseshoe bat (Rhinolophus ferrumequinum). J Exp Biol. 2016; 219(Pt 6):834-43. DOI: 10.1242/jeb.133272. View

17.

Zani P, Irwin J, Rollyson M, Counihan J, Healas S, Lloyd E . Glycogen, not dehydration or lipids, limits winter survival of side-blotched lizards (Uta stansburiana). J Exp Biol. 2012; 215(Pt 17):3126-34. DOI: 10.1242/jeb.069617. View

18.

Biggar Y, Storey K . Global DNA modifications suppress transcription in brown adipose tissue during hibernation. Cryobiology. 2014; 69(2):333-8. DOI: 10.1016/j.cryobiol.2014.08.008. View

19.

Luan Y, Ou J, Kunze V, Qiao F, Wang Y, Wei L . Integrated transcriptomic and metabolomic analysis reveals adaptive changes of hibernating retinas. J Cell Physiol. 2017; 233(2):1434-1445. DOI: 10.1002/jcp.26030. View

20.

Nespolo R, Gaitan-Espitia J, Quintero-Galvis J, Fernandez F, Silva A, Molina C . A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides reveals adaptive regulation of protective functions during hibernation. Mol Ecol. 2018; 27(22):4489-4500. DOI: 10.1111/mec.14876. View