{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:47:49Z","timestamp":1782535669766,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFD1302000"],"award-info":[{"award-number":["2023YFD1302000"]}]},{"name":"Jilin Provincial Standardization Project","award":["DBXM088-2024"],"award-info":[{"award-number":["DBXM088-2024"]}]},{"name":"Jilin Provincial Post-subsidy Project for Excellent Breeds of Livestock and Poultry","award":["20250339"],"award-info":[{"award-number":["20250339"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>White adipose tissue (WAT) is essential for maintaining energy homeostasis during hibernation by supplying lipolysis-derived fatty acids as a major fuel source. In raccoon dogs (Nyctereutes procyonoides), the activity of brown adipose tissue is diminished, providing a unique model to investigate how WAT supports metabolic homeostasis in a largely non-thermogenic state. Here, we integrated physiological, histological, transcriptomic, and molecular analyses of back-fat and tail-fat depots during autumn fattening and winter sleep. Despite reduced food intake, body weight loss, and mild hypothermia, raccoon dogs maintained systemic glucose and lipid homeostasis. Both WAT depots exhibited adipocyte atrophy and the coordinated suppression of core metabolic and biosynthetic pathways, indicating a shared program of metabolic depression. However, the two depots adopted distinct remodeling strategies. Back-fat showed collagen densification and vascular-associated remodeling, suggesting a structural adaptation that may preserve tissue integrity during winter sleep. In contrast, tail-fat displayed enhanced innate immune signaling and M2 macrophage enrichment, indicating immune niche remodeling that may support tissue protection during prolonged lipid mobilization. Together, these findings reveal that raccoon dogs maintain metabolic homeostasis during shallow hibernation through a non-thermogenic, WAT-centered strategy characterized by shared metabolic depression and depot-specific structural and immunometabolic remodeling.<\/jats:p>","DOI":"10.3390\/ijms27125611","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Depot-Specific White Adipose Tissue Remodeling Supports Non-Thermogenic Metabolic Homeostasis During Shallow Hibernation in Raccoon Dogs"],"prefix":"10.3390","volume":"27","author":[{"given":"Ruojun","family":"Zong","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agriculture University, Changchun 130118, China"},{"name":"State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Han","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agriculture University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runzhou","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manman","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agriculture University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agriculture University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agriculture University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Du","sequence":"additional","affiliation":[{"name":"College of Agriculture, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2770-3913","authenticated-orcid":false,"given":"Chao","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Jilin Agriculture University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.4093\/dmj.2023.0011","article-title":"Adipose Tissue and Metabolic Health","volume":"47","author":"An","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"load021","DOI":"10.1093\/lifemeta\/load021","article-title":"Extracellular matrix remodelling in obesity and metabolic disorders","volume":"2","author":"Musale","year":"2023","journal-title":"Life Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"C375","DOI":"10.1152\/ajpcell.00379.2020","article-title":"Adipose tissue inflammation and metabolic dysfunction in obesity","volume":"320","author":"Kawai","year":"2020","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"116324","DOI":"10.1016\/j.bcp.2024.116324","article-title":"Interrelation of adipose tissue macrophages and fibrosis in obesity","volume":"225","author":"Dahdah","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1146\/annurev.nutr.25.050304.092514","article-title":"Annual lipid cycles in hibernators: Integration of physiology and behavior","volume":"25","author":"Dark","year":"2005","journal-title":"Annu Rev. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1152\/physrev.00008.2003","article-title":"Mammalian hibernation: Cellular and molecular responses to depressed metabolism and low temperature","volume":"83","author":"Carey","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1080\/07420520701797999","article-title":"Seasonal rhythms of body temperature in the free-ranging raccoon dog (Nyctereutes procyonoides) with special emphasis on winter sleep","volume":"24","author":"Mustonen","year":"2007","journal-title":"Chronobiol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/czoolo\/57.5.584","article-title":"Invasion of the raccoon dog Nyctereutes procyonoides in Europe: History of colonization, features behind its success, and threats to native fauna","volume":"57","author":"Kauhala","year":"2011","journal-title":"Curr. Zool."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"R188","DOI":"10.1016\/j.cub.2013.01.062","article-title":"Hibernation","volume":"23","author":"Geiser","year":"2013","journal-title":"Curr. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2108\/zsj.21.385","article-title":"Seasonal physiology of the wild raccoon dog (Nyctereutes procyonoides)","volume":"21","author":"Asikainen","year":"2004","journal-title":"Zool. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00360-017-1114-5","article-title":"A review of the physiology of a survival expert of big freeze, deep snow, and an empty stomach: The boreal raccoon dog (Nyctereutes procyonoides)","volume":"188","author":"Mustonen","year":"2018","journal-title":"J. Comp. Physiol. B"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/jez.a.126","article-title":"Endocrine response to fasting in the overwintering captive raccoon dog (Nyctereutes procyonoides)","volume":"301","author":"Nieminen","year":"2004","journal-title":"J. Exp. Zool. A Comp. Exp. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1046\/j.1439-0396.2002.00389.x","article-title":"Reproduction of the raccoon dog (Nyctereutes procyonoides) after feeding or food deprivation in winter","volume":"86","author":"Asikainen","year":"2002","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"jeb160606","DOI":"10.1242\/jeb.160606","article-title":"Molecular interactions underpinning the phenotype of hibernation in mammals","volume":"222","author":"Andrews","year":"2019","journal-title":"J. Exp. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/s42003-019-0574-4","article-title":"Hibernation induces widespread transcriptional remodeling in metabolic tissues of the grizzly bear","volume":"2","author":"Jansen","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_16","first-page":"2196","article-title":"Raccoon dog model shows preservation of bone during prolonged catabolism and reduced physical activity","volume":"220","author":"Mustonen","year":"2017","journal-title":"J. Exp. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chen, D., Guo, X., Wang, K., Zhao, W., Chang, Z., Wang, Q., and Xu, C. (2023). Multi-Omics Analysis Reveals the Pathogenesis of Growth-Disordered Raccoon Dog. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814237"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Choe, S.S., Huh, J.Y., Hwang, I.J., Kim, J.I., and Kim, J.B. (2016). Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. Front. Endocrinol., 7.","DOI":"10.3389\/fendo.2016.00030"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1007\/s11745-007-3118-5","article-title":"Selective seasonal fatty acid accumulation and mobilization in the wild raccoon dog (Nyctereutes procyonoides)","volume":"42","author":"Mustonen","year":"2007","journal-title":"Lipids"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/jez.a.10299","article-title":"Seasonal reproductive endocrine profile of the raccoon dog (Nyctereutes procyonoides)-effects of melatonin and food deprivation","volume":"299","author":"Asikainen","year":"2003","journal-title":"J. Exp. Zool. A Comp. Exp. Biol."},{"key":"ref_21","first-page":"1","article-title":"Physiological adaptations of the raccoon dog (Nyctereutes procyonoides) to seasonal fasting-fat and nitrogen metabolism and influence of continuous melatonin treatment","volume":"174","author":"Mustonen","year":"2004","journal-title":"J. Comp. Physiol. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"jeb162586","DOI":"10.1242\/jeb.162586","article-title":"Nature\u2019s fat-burning machine: Brown adipose tissue in a hibernating mammal","volume":"221","author":"Ballinger","year":"2018","journal-title":"J. Exp. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hampton, M., Melvin, R.G., and Andrews, M.T. (2013). Transcriptomic analysis of brown adipose tissue across the physiological extremes of natural hibernation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0085157"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Niiranen, L., Makela, K.A., Mutt, S.J., Viitanen, R., Kaisanlahti, A., Vicente, D., Noponen, T., Autio, A., Roivainen, A., and Nuutila, P. (2021). Role of Brown and Beige Adipose Tissues in Seasonal Adaptation in the Raccoon Dog (Nyctereutes procyonoides). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179623"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"139","DOI":"10.4098\/AT.arch.93-12","article-title":"Growth, size, and fat reserves of the raccoon dog in Finland","volume":"38","author":"Kauhala","year":"1993","journal-title":"Acta Theriol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s42003-023-04523-9","article-title":"Whole-body adipose tissue multi-omic analyses in sheep reveal molecular mechanisms underlying local adaptation to extreme environments","volume":"6","author":"Xu","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chayama, Y., Ando, L., Sato, Y., Shigenobu, S., Anegawa, D., Fujimoto, T., Taii, H., Tamura, Y., Miura, M., and Yamaguchi, Y. (2018). Molecular Basis of White Adipose Tissue Remodeling That Precedes and Coincides with Hibernation in the Syrian Hamster, a Food-Storing Hibernator. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01973"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101265","DOI":"10.1016\/j.molmet.2021.101265","article-title":"Hepatocyte-specific glucose-6-phosphatase deficiency disturbs platelet aggregation and decreases blood monocytes upon fasting-induced hypoglycemia","volume":"53","author":"Bazioti","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1146\/annurev.biochem.66.1.581","article-title":"Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression","volume":"66","author":"Hanson","year":"1997","journal-title":"Annu. Rev. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jhep.2013.02.020","article-title":"PEPCK-M expression in mouse liver potentiates, not replaces, PEPCK-C mediated gluconeogenesis","volume":"59","author":"Duarte","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.molcel.2015.09.025","article-title":"PEPCK Coordinates the Regulation of Central Carbon Metabolism to Promote Cancer Cell Growth","volume":"60","author":"Montal","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-Carbon Metabolism in Health and Disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1700262","DOI":"10.1002\/mnfr.201700262","article-title":"Serine alleviates oxidative stress via supporting glutathione synthesis and methionine cycle in mice","volume":"61","author":"Zhou","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.molcel.2015.12.014","article-title":"Serine Metabolism Supports the Methionine Cycle and DNA\/RNA Methylation through De Novo ATP Synthesis in Cancer Cells","volume":"61","author":"Maddocks","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.cmet.2013.06.016","article-title":"Fibrosis and adipose tissue dysfunction","volume":"18","author":"Sun","year":"2013","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.tcb.2022.02.008","article-title":"Extracellular matrix remodeling facilitates obesity-associated cancer progression","volume":"32","author":"Kim","year":"2022","journal-title":"Trends Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109975","DOI":"10.1016\/j.cellsig.2021.109975","article-title":"Markers of tissue remodeling and inflammation in the white and brown adipose tissues of a model hibernator","volume":"82","author":"Logan","year":"2021","journal-title":"Cell Signal"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.it.2017.03.001","article-title":"Macrophage Immunometabolism: Where Are We (Going)?","volume":"38","author":"Menon","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/ni.2956","article-title":"Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages","volume":"15","author":"Huang","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.immuni.2016.09.016","article-title":"Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation","volume":"45","author":"Huang","year":"2016","journal-title":"Immunity"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5611\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:32:08Z","timestamp":1782534728000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125611"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125611","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]}}}