{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:49:59Z","timestamp":1785761399982,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170457"],"award-info":[{"award-number":["32170457"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32170457"],"award-info":[{"award-number":["32170457"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Food scarcity is a major ecological challenge for cavefish; however, their coordinated physiological and molecular responses to prolonged starvation remain poorly understood. Here, we characterized the responses of Triplophysa rosa to 30, 60, and 90 days of food deprivation under controlled laboratory conditions by integrating growth measurements, histology, transcriptomics, quantitative reverse transcription PCR, and transmission electron microscopy. Starvation inhibited growth, reduced the condition factor and hepatosomatic index, and induced hepatocyte shrinkage, consistent with mobilization of hepatic energy reserves. Liver genes with declining temporal expression were enriched mainly in lipid biosynthesis, cholesterol metabolism, ribosomal function, and cell-cycle pathways, consistent with reduced biosynthetic activity. In the spleen, immune-related transcription increased during early starvation and declined at later stages, while the greater prominence of melano-macrophage centers was consistent with greater involvement of cellular clearance and tissue maintenance during prolonged starvation. Prolonged starvation also increased the expression of autophagy-related genes in the liver and spleen, and autophagy-related structures became more prominent in representative transmission electron microscopy images, consistent with increased involvement of intracellular recycling. Together, these findings reveal a coordinated temporal response involving metabolic adjustment, stage-dependent reorganization of splenic immune-related processes, and autophagy-associated cellular maintenance in T. rosa. This integrated approach improves our understanding of physiological maintenance during sustained nutrient limitation in cave-restricted fish.<\/jats:p>","DOI":"10.3390\/biology15151273","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:50:21Z","timestamp":1785757821000},"page":"1273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Histological and Transcriptomic Characterization of Prolonged Starvation Responses in the Cavefish Triplophysa rosa"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1511-9853","authenticated-orcid":false,"given":"Zechen","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Southwest University School of Life Sciences, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyun","family":"Ni","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Southwest University School of Life Sciences, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Southwest University School of Life Sciences, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9539-103X","authenticated-orcid":false,"given":"Yongming","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Southwest University School of Life Sciences, Chongqing 400715, China"},{"name":"Fishes Conservation and Utilization in the Upper Reaches of the Yangtze River Key Laboratory of Sichuan Province, Neijiang Normal University College of Fisheries, Neijiang 641100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4648-2493","authenticated-orcid":false,"given":"Feng","family":"Shao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Southwest University School of Life Sciences, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-2025","authenticated-orcid":false,"given":"Zuogang","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Southwest University School of Life Sciences, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1139\/f04-083","article-title":"Over-winter lipid depletion and mortality of age-0 rainbow trout (Oncorhynchus mykiss)","volume":"61","author":"Biro","year":"2004","journal-title":"Can. J. Fish. Aquat. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Qian, B., Xue, L., and Huang, H. (2016). Liver transcriptome analysis of the large yellow croaker (Larimichthys crocea) during fasting by using RNA-seq. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150240"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1152\/physrev.00015.2006","article-title":"Endoplasmic reticulum stress signaling in disease","volume":"86","author":"Marciniak","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/BF00004651","article-title":"Protein synthesis in trout liver is stimulated by both feeding and fasting","volume":"10","author":"McMillan","year":"1992","journal-title":"Fish Physiol. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Shi, J., Zhuo, D., Lu, M., Wang, H., Gu, H., Liu, X., and Wang, Z. (2023). Partial immune responses in Sichuan bream (Sinibrama taeniatus) after starvation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1098741"},{"key":"ref_6","first-page":"91","article-title":"Effects of starvation on the non-specific immune parameters of grass carp, Ctenopharyngodon idellus","volume":"47","author":"Jun","year":"2012","journal-title":"Chin. J. Zool."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Martin, S.A., Douglas, A., Houlihan, D.F., and Secombes, C.J. (2010). Starvation alters the liver transcriptome of the innate immune response in Atlantic salmon (Salmo salar). BMC Genom., 11.","DOI":"10.1186\/1471-2164-11-418"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, M., Xu, G., Tang, Y., Su, S., Wang, Y., and Zhu, Z. (2021). Investigation of the molecular mechanisms of antioxidant damage and immune response downregulation in liver of Coilia nasus under starvation stress. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.622315"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1467-8721.2007.00522.x","article-title":"Stress, energy, and immunity: An ecological view","volume":"16","author":"Segerstrom","year":"2007","journal-title":"Curr. Dir. Psychol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1042\/BJ20111451","article-title":"Autophagy, mitochondria and oxidative stress: Cross-talk and redox signalling","volume":"441","author":"Lee","year":"2012","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1641\/0006-3568(2002)052[0473:SEATFB]2.0.CO;2","article-title":"Subterranean ecosystems: A truncated functional biodiversity","volume":"52","author":"Gibert","year":"2002","journal-title":"Bioscience"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1365-2435.2010.01800.x","article-title":"Trade-off between growth and immune function: A meta-analysis of selection experiments","volume":"25","author":"Parmentier","year":"2011","journal-title":"Funct. Ecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.0022-1112.2005.00622.x","article-title":"Triplophysa rosa sp. nov.: A new blind loach from China","volume":"66","author":"Chen","year":"2005","journal-title":"J. Fish Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"740395","DOI":"10.1016\/j.aquaculture.2023.740395","article-title":"The cavefish Triplophysa rosa has a well-developed adaptive immune system: Evidence from histological and comparative genomic analysis","volume":"581","author":"Ni","year":"2024","journal-title":"Aquaculture"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1007\/s00360-018-1178-x","article-title":"Body and organ metabolic rates of a cave fish, Triplophysa rosa: Influence of light and ontogenetic variation","volume":"188","author":"Shi","year":"2018","journal-title":"J. Comp. Physiol. B-Biochem. Syst. Environ. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5831","DOI":"10.1111\/mec.16700","article-title":"Novel genome sequence of Chinese cavefish (Triplophysa rosa) reveals pervasive relaxation of natural selection in cavefish genomes","volume":"31","author":"Zhao","year":"2022","journal-title":"Mol. Ecol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhao, Q., Zhang, R., Xiao, Y., Niu, Y., Shao, F., Li, Y., and Peng, Z. (2020). Comparative transcriptome profiling of the loaches Triplophysa bleekeri and Triplophysa rosa reveals potential mechanisms of eye degeneration. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01334"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1038\/s41559-020-1234-2","article-title":"Adaptation to low parasite abundance affects immune investment and immunopathological responses of cavefish","volume":"4","author":"Box","year":"2020","journal-title":"Nat. Ecol. Evol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1255833","DOI":"10.1080\/19420889.2016.1255833","article-title":"A genomic survey on the immune differences among Sinocyclocheilus fishes","volume":"9","author":"Qiu","year":"2016","journal-title":"Commun. Integr. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Buchmann, K., and Secombes, C.J. (2022). Principles of Fish Immunology: From Cells and Molecules to Host Protection, Springer Nature.","DOI":"10.1007\/978-3-030-85420-1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nbt.3122","article-title":"StringTie enables improved reconstruction of a transcriptome from RNA-seq reads","volume":"33","author":"Pertea","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ernst, J., and Bar-Joseph, Z. (2006). STEM: A tool for the analysis of short time series gene expression data. BMC Bioinform., 7.","DOI":"10.1186\/1471-2105-7-191"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9668","DOI":"10.1073\/pnas.1510802112","article-title":"Melanocortin 4 receptor mutations contribute to the adaptation of cavefish to nutrient-poor conditions","volume":"112","author":"Aspiras","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ydbio.2018.06.003","article-title":"Early adipogenesis contributes to excess fat accumulation in cave populations of Astyanax mexicanus","volume":"441","author":"Xiong","year":"2018","journal-title":"Dev. Biol."},{"key":"ref_29","unstructured":"Tian, W. (2022). Effects of Starvation Stress on Immune Function of Megalobrama amblycephala and Danio rerio. [Master\u2019s Thesis, Huazhong Agricultural University]."},{"key":"ref_30","unstructured":"Chen, P. (2006). Effects of Starvation and Refeeding on the Activity of Digestive Enzymes, Feeding and Growth, Biochemical Composition of Erythroculter ilishaeformis Juvenile. [Master\u2019s Thesis, Huazhong Agricultural University]."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbpa.2010.01.002","article-title":"Starvation physiology: Reviewing the different strategies animals use to survive a common challenge","volume":"156","author":"McCue","year":"2010","journal-title":"Comp. Biochem. Physiol. A-Mol. Integr. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/jfb.15630","article-title":"Evaluation of starvation status in the early developmental stages of black rockfish (Sebastes schlegelii) based on morphological and histological characteristics","volume":"106","author":"Guo","year":"2025","journal-title":"J. Fish Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1152\/physiolgenomics.90213.2008","article-title":"Effect of starvation on transcriptomes of brain and liver in adult female zebrafish (Danio rerio)","volume":"35","author":"Drew","year":"2008","journal-title":"Physiol. Genom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1152\/physiolgenomics.00203.2003","article-title":"Starvation response in mouse liver shows strong correlation with life-span-prolonging processes","volume":"17","author":"Bauer","year":"2004","journal-title":"Physiol. Genom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/ajcn\/74.5.670","article-title":"Specific and nonspecific immune responses to fasting and refeeding differ in healthy young adult and elderly persons","volume":"74","author":"Walrand","year":"2001","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1126\/science.1173635","article-title":"Caloric restriction delays disease onset and mortality in rhesus monkeys","volume":"325","author":"Colman","year":"2009","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.cmet.2013.12.008","article-title":"Fasting: Molecular mechanisms and clinical applications","volume":"19","author":"Longo","year":"2014","journal-title":"Cell Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/(SICI)1097-4652(199907)180:1<123::AID-JCP14>3.0.CO;2-W","article-title":"Cellular proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta)","volume":"180","author":"Pendergrass","year":"1999","journal-title":"J. Cell. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.cmet.2020.01.015","article-title":"AMPK and TOR: The yin and yang of cellular nutrient sensing and growth control","volume":"31","author":"Hall","year":"2020","journal-title":"Cell Metab."},{"key":"ref_40","unstructured":"Fan, X. (2020). The Effects of Starvation Stress on Reproduction, Cell Growth, Autophagy, and DNA Methylation Responsive Mechanism in Zebrafish (Danio rerio). [Doctoral Dissertation, Northwest A&F University]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/S0531-5565(03)00161-X","article-title":"Life extension via dietary restriction is independent of the Ins\/IGF-1 signalling pathway in Caenorhabditis elegans","volume":"38","author":"Houthoofd","year":"2003","journal-title":"Exp. Gerontol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/15\/1273\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:08:33Z","timestamp":1785758913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/15\/1273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":41,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["biology15151273"],"URL":"https:\/\/doi.org\/10.3390\/biology15151273","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}