{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:21:32Z","timestamp":1787728892765,"version":"build-2784847793"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007194","name":"Wenzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["Y2023067"],"award-info":[{"award-number":["Y2023067"]}],"id":[{"id":"10.13039\/501100007194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900778"],"award-info":[{"award-number":["81900778"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY21H070004"],"award-info":[{"award-number":["LY21H070004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022955","name":"Fundamental Research Funds for the Provincial Universities of Zhejiang","doi-asserted-by":"publisher","award":["KYYW202103"],"award-info":[{"award-number":["KYYW202103"]}],"id":[{"id":"10.13039\/100022955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adipose tissue remodelling, encompassing white adipose tissue (WAT) browning alongside brown adipose tissue (BAT) activation, holds promise for combating obesity, yet the endogenous chemokine receptors that restrain this plasticity remain ill\u2010defined. Here, we uncover that C\u2012C chemokine receptor 1 (CCR1) restrains adipocyte remodelling and energy expenditure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A high\u2010fat diet (HFD) was provided to systemic and adipocyte\u2010specific\u00a0\n                      <jats:italic>Ccr1<\/jats:italic>\n                      \u00a0knockout mice. The CCR1\u2010selective antagonist BX471 was administered to HFD\u2010fed wild\u2010type (WT) mice as a preventive regimen. Energy expenditure was assessed via indirect calorimetry; BAT thermogenic activity and WAT beiging were quantified through histology and gene expressin analyses. Adipose tissue macrophage homeostasis was analysed via flow cytometry. Peritoneal macrophages were differentiated into either the M1 or M2 state, and conditioned media were applied to the adipocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In HFD\u2010fed mice,\n                      <jats:italic>Ccr1<\/jats:italic>\n                      \u00a0ablation conferred resistance to obesity and insulin resistance, coupled with enhanced WAT browning, augmented BAT thermogenesis and elevated energy expenditure. These metabolic benefits were associated with a shift towards M2 macrophage polarisation and reduced adipose tissue inflammation. Adipocyte\u2010specific\u00a0\n                      <jats:italic>Ccr1<\/jats:italic>\n                      \u00a0knockout recapitulated these phenotypes. BX471 administration in WT mice phenocopied the metabolic effects of\n                      <jats:italic>Ccr1<\/jats:italic>\n                      deficiency under HFD conditions. Mechanistically, in vitro experiments suggested that\n                      <jats:italic>Ccr1<\/jats:italic>\n                      loss suppressed G\u03b1i\u2010dependent signalling, leading to increased intracellular cyclic adenosine monophosphate (cAMP) and subsequent protein kinase A\/cAMP\u2010response element\u2010binding protein 1 (PKA\/CREB) activation, thereby promoting thermogenic gene expression in adipocytes. In addition, conditioned media from M2\u2010polarised macrophages enhanced thermogenic gene expression in adipocytes, and this effect was further potentiated in\n                      <jats:italic>Ccr1<\/jats:italic>\n                      \u2010deficient adipocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CCR1 regulates adipose tissue remodelling and systemic energy expenditure, at least in part, through cAMP\/PKA\/CREB signalling and macrophage homeostasis. Pharmacological inhibition of CCR1 attenuates obesity development, suggesting a potential preventive strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>CCR1 expression is significantly elevated in adipose tissue of obese individuals.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Systemic and adipocyte\u2010specific\n                            <jats:italic>Ccr1<\/jats:italic>\n                            deletion promotes fat browning via cAMP\/PKA\/CREB activation and M2 macrophage polarisation, protecting against obesity.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pharmacological blockade of CCR1 suppresses obesity progression, highlighting its potential as a novel target for metabolic disorders.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70762","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T07:46:45Z","timestamp":1786002405000},"source":"Crossref","is-referenced-by-count":0,"title":["Chemokine receptor CCR1 restrains adipose tissue remodelling via cAMP\/PKA\/CREB signalling and adipocyte\u2012macrophage crosstalk in mice"],"prefix":"10.1002","volume":"16","author":[{"given":"Suili","family":"Cai","sequence":"first","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengchen","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengru","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Dai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengru","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Cixi Biomedical Research Institute, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00769-z"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-024-06102-x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02403-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.01.026"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2023.0011"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2023.101683"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.93151.3"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.05.028"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58060761"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom5031563"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413528"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.07.015"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20210959"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-021-00918-z"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155758"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2630"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1375"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41387-022-00222-2"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/21623945.2021.1906510"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqab064"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154914"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35335-w"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.016"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01311-9"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2005.01.018"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00411.2010"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3786-2"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2015.10.005"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2003"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.60354"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2016.11.005"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01572-3"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.05.014"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.503797"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01149-x"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45899-4"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14115"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-19-0190"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.066"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10653"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105030"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753425920975082"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010128"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.04.003"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70762","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ctm2.70762","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70762","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:40:14Z","timestamp":1787726414000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.70762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ctm2.70762"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.70762","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"article-number":"e70762"}}