{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:03:24Z","timestamp":1789466604912,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Heilongjiang Province Natural Science Foundation","doi-asserted-by":"crossref","award":["JQ2024C004"],"award-info":[{"award-number":["JQ2024C004"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100015242","name":"National Swine Industry Technology System","doi-asserted-by":"crossref","award":["CARS-34"],"award-info":[{"award-number":["CARS-34"]}],"id":[{"id":"10.13039\/501100015242","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Heilongjiang Provincial Research Institutes Research Business Fund Project","award":["CZKYF2026-1-C018"],"award-info":[{"award-number":["CZKYF2026-1-C018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cold exposure is a major physiological stimulus that promotes adipose tissue browning and enhances thermogenic capacity. As a cold-tolerant breed, Min pigs may rely on distinct adaptive mechanisms in adipose tissues, but how different adipose depots respond to cold stress remains unclear. This study systematically examines how cold exposure affects adipose tissue morphology, thermogenic gene expression, and the differentiation potential of preadipocytes derived from four adipose depots\u2014cervical, axillary, perirenal, and inguinal\u2014in Min pigs. Adipose tissues from the four depots were collected and analyzed using infrared thermography, histological staining, scanning electron microscopy, real-time quantitative PCR, Western blotting and in vitro differentiation assays. The results demonstrated that cold stress induced depot-specific remodeling patterns. Infrared thermography showed that the subcutaneous adipose depots including inguinal and axillary depots maintained relatively higher surface temperatures following cold exposure. Histological and ultrastructural analyses revealed typical beige-like characteristics in inguinal depots, including the accumulation of small lipid droplets, whereas changes in other depots were minimal. Molecular analyses further confirmed this heterogeneity: inguinal depots exhibited the strongest beiging response, characterized by significant upregulation of key thermogenic markers (PGC1\u03b1, UCP3, and DIO2) and lipolytic genes (HSL and ATGL) at the mRNA and\/or protein levels. In contrast, visceral adipose depots showed weak or suppressed thermogenic activation. In vitro differentiation assays demonstrated that preadipocytes isolated from inguinal depot had the strongest beiging potential, forming tightly packed small lipid droplets and markedly increasing the expression of beige adipose-related genes upon induction. In conclusion, this study demonstrates that cold stress induces distinct beige remodeling across adipose depots in Min pigs, with the inguinal depot exhibiting the strongest thermogenic response and differentiation potential at morphological, molecular, and cellular levels. These findings identify the inguinal depot as a key site for adaptive thermogenesis and provide novel insights into adipose tissue remodeling and environmental adaptation in large mammals.<\/jats:p>","DOI":"10.3390\/cells15181661","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:16:48Z","timestamp":1789460208000},"page":"1661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Cold Stress on the Morphology and Thermogenic Capacity of Adipose Tissue in Various Anatomical Depots of Min\u00a0pigs"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9512-7730","authenticated-orcid":false,"given":"Shuo","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, 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(2013). Mechanism of Storage and Synthesis of Fatty Acids and Triglycerides in White Adipocytes. Physiology and Physiopathology of Adipose Tissue, Springer.","DOI":"10.1007\/978-2-8178-0343-2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16616","DOI":"10.1074\/jbc.M117.790451","article-title":"Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice","volume":"292","author":"Bal","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nrm.2016.96","article-title":"Control of brown and beige fat development","volume":"17","author":"Wang","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0378-1119(00)00061-5","article-title":"First evidence of uncoupling protein-2 (UCP-2) and -3 (UCP-3) gene expression in piglet skeletal muscle and adipose tissue","volume":"246","author":"Damon","year":"2000","journal-title":"Gene"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.gene.2017.11.074","article-title":"Genome-wide profiling of gene expression and DNA methylation provides insight into low-altitude acclimation in Tibetan pigs","volume":"642","author":"Jin","year":"2018","journal-title":"Gene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1016\/j.celrep.2019.07.030","article-title":"ATGL\/CGI-58-Dependent Hydrolysis of a Lipid Storage Pool in Murine Enterocytes","volume":"28","author":"Korbelius","year":"2019","journal-title":"Cell Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"C269","DOI":"10.1152\/ajpcell.00126.2016","article-title":"Reduced ATGL-mediated lipolysis attenuates \u03b2-adrenergic-induced AMPK signaling, but not the induction of PKA-targeted genes, in adipocytes and adipose tissue","volume":"311","author":"MacPherson","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kim, S., Yazawa, T., Koide, A., Yoneda, E., Aoki, R., Okazaki, T., Tomita, K., Watanabe, H., Muroi, Y., and Testuka, M. (2024). Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway. Biology, 13.","DOI":"10.3390\/biology13050284"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"467","DOI":"10.4252\/wjsc.v6.i4.467","article-title":"Human induced pluripotent stem cells: A new source for brown and white adipocytes","volume":"6","author":"Hafner","year":"2014","journal-title":"World J. Stem Cells"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yao, X., Dani, V., and Dani, C. (2020). Human Pluripotent Stem Cells: A Relevant Model to Identify Pathways Governing Thermogenic Adipocyte Generation. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00932"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1038\/nm.3324","article-title":"Tracking adipogenesis during white adipose tissue development, expansion and regeneration","volume":"19","author":"Wang","year":"2013","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E1244","DOI":"10.1152\/ajpendo.00600.2009","article-title":"The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation","volume":"298","author":"Barbatelli","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"C670","DOI":"10.1152\/ajpcell.2000.279.3.C670","article-title":"Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes","volume":"279","author":"Melnyk","year":"2000","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1093\/jmcb\/mjx018","article-title":"Cold adaptation in pigs depends on UCP3 in beige adipocytes","volume":"9","author":"Lin","year":"2017","journal-title":"J. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, L.L., Hu, S.L., Cao, C.W., Chen, C.H., Liu, J.L., Wang, Y., Liu, J.F., Zhao, J.G., Tao, C., and Wang, Y.F. (2022). Functional and Genetic Characterization of Porcine Beige Adipocytes. Cells, 11.","DOI":"10.3390\/cells11040751"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e14556","DOI":"10.7717\/peerj.14556","article-title":"Differences in histomorphology and expression of key lipid regulated genes of four adipose tissues from Tibetan pigs","volume":"11","author":"Lin","year":"2023","journal-title":"PeerJ"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zuriaga, M.A., Fuster, J.J., Gokce, N., and Walsh, K. (2017). Humans and Mice Display Opposing Patterns of \u201cBrowning\u201d Gene Expression in Visceral and Subcutaneous White Adipose Tissue Depots. Front. Cardiovasc. Med., 4.","DOI":"10.3389\/fcvm.2017.00027"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109023","DOI":"10.1016\/j.celrep.2021.109023","article-title":"Quantification of adipocyte numbers following adipose tissue remodeling","volume":"35","author":"Moser","year":"2021","journal-title":"Cell Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, Y., Shi, H.X., Li, J., Du, H., Jia, R., Liang, Y.H., Huang, X.Y., Gao, X.L., Gun, S.B., and Yang, Q.L. (2025). Adaptive Thermogenesis and Lipid Metabolism Modulation in Inguinal and Perirenal Adipose Tissues of Hezuo Pigs in Response to Low-Temperature Exposure. Cells, 14.","DOI":"10.3390\/cells14060392"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2041731419888168","DOI":"10.1177\/2041731419888168","article-title":"Biochemical and biomechanical comparisions of decellularized scaffolds derived from porcine subcutaneous and visceral adipose tissue","volume":"10","author":"Lin","year":"2019","journal-title":"J. Tissue Eng."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.cmet.2010.02.013","article-title":"Gs\u03b1 deficiency in adipose tissue leads to a lean phenotype with divergent effects on cold tolerance and diet-induced thermogenesis","volume":"11","author":"Chen","year":"2010","journal-title":"Cell Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1101\/gad.311969.118","article-title":"Impaired DNA demethylation of C\/EBP sites causes premature aging","volume":"32","author":"Mekker","year":"2018","journal-title":"Genes Dev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.celrep.2018.06.073","article-title":"Cold-Activated Lipid Dynamics in Adipose Tissue Highlights a Role for Cardiolipin in Thermogenic Metabolism","volume":"24","author":"Lynes","year":"2018","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.cmet.2016.06.011","article-title":"Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation","volume":"24","author":"Ramage","year":"2016","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pan, R., Zhu, X., Maretich, P., and Chen, Y. (2020). Metabolic Improvement via Enhancing Thermogenic Fat-Mediated Non-shivering Thermogenesis: From Rodents to Humans. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00633"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Liu, J., Jiang, Y., Liu, T., Chen, C., Chui, L., Cui, A., Zhang, X., Wang, X., Wang, Y., and Yang, C. (2025). Single-nucleus RNA sequencing defines adipose tissue subpopulations that contribute to Tibetan pig cold adaptation. BMC Biol., 23.","DOI":"10.1186\/s12915-025-02211-0"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R97","DOI":"10.1530\/JOE-18-0598","article-title":"Adipose tissue browning in mice and humans","volume":"241","author":"Herz","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yang, S., Ma, H., Wang, L., Wang, F., Xia, J.Q., Liu, D.Y., Mu, L.L., Yang, X.Q., and Liu, D. (2024). The Role of \u03b23-Adrenergic Receptors in Cold-Induced Beige Adipocyte Production in Pigs. Cells, 13.","DOI":"10.3390\/cells13080709"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1113\/JP285269","article-title":"Adipose tissue browning and thermogenesis under physiologically energetic challenges: A remodelled thermogenic system","volume":"602","author":"Zhu","year":"2024","journal-title":"J. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1038\/sj.ijo.0802905","article-title":"Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-\u03b1","volume":"29","author":"Puigserver","year":"2005","journal-title":"Int. J. Obes."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1042\/BCJ20190463","article-title":"UCP1-independent thermogenesis","volume":"477","author":"Roesler","year":"2020","journal-title":"Biochem. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/s41580-021-00350-0","article-title":"The cellular and functional complexity of thermogenic fat","volume":"22","author":"Cohen","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1016\/j.celrep.2020.02.023","article-title":"Early B Cell Factor Activity Controls Developmental and Adaptive Thermogenic Gene Programming in Adipocytes","volume":"30","author":"Angueira","year":"2020","journal-title":"Cell Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1111\/iju.70158","article-title":"Perirenal Fat in Disease Progression: From Inflammatory Mediator to Therapeutic Target","volume":"32","author":"Kashiwagi","year":"2025","journal-title":"Int. J. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1038\/sj.ijo.0802907","article-title":"Regulation of PPAR\u03b3 activity during adipogenesis","volume":"29","author":"Farmer","year":"2005","journal-title":"Int. J. Obes."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/2045-3701-4-29","article-title":"Transcriptional and epigenetic regulation of PPAR\u03b3 expression during adipogenesis","volume":"4","author":"Lee","year":"2014","journal-title":"Cell Biosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/s41574-024-01071-y","article-title":"Enhancing adipose tissue plasticity: Progenitor cell roles in metabolic health","volume":"21","author":"Lecoutre","year":"2025","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mo, Y.-Y., Han, Y.-X., Xu, S.-N., Jiang, H.-L., Wu, H.-X., Cai, J.-M., Li, L., Bu, Y.-H., Xiao, F., and Liang, H.-D. (2024). Adipose Tissue Plasticity: A Comprehensive Definition and Multidimensional Insight. Biomolecules, 14.","DOI":"10.3390\/biom14101223"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/cdd.2014.148","article-title":"Depletion of white adipocyte progenitors induces beige adipocyte differentiation and suppresses obesity development","volume":"22","author":"Daquinag","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12152","DOI":"10.1038\/ncomms12152","article-title":"Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat","volume":"7","author":"Seki","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_42","first-page":"E372","article-title":"Lipid metabolism and secretory function of porcine intramuscular adipocytes compared with subcutaneous and perirenal adipocytes","volume":"291","author":"Gardan","year":"2006","journal-title":"Am. J. Physiol. Metab."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1661\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:36:34Z","timestamp":1789461394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1661"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":42,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cells15181661"],"URL":"https:\/\/doi.org\/10.3390\/cells15181661","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}