{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T03:37:41Z","timestamp":1774064261753,"version":"3.50.1"},"reference-count":33,"publisher":"Korean Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C3004843"],"award-info":[{"award-number":["2020R1A2C3004843"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022M3E5E8017213"],"award-info":[{"award-number":["2022M3E5E8017213"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1C1C1012590"],"award-info":[{"award-number":["2022R1C1C1012590"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1C1C1004187"],"award-info":[{"award-number":["2022R1C1C1004187"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["RS-2024-00438349"],"award-info":[{"award-number":["RS-2024-00438349"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["RS-2024-00404132"],"award-info":[{"award-number":["RS-2024-00404132"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:p>Background: Chronic low-grade inflammation in multiple metabolic organs contributes to the development of insulin resistance induced by obesity. Progranulin (PGRN) is an evolutionarily-conserved secretory protein implicated in immune modulation. The generalized deletion of the PGRN-encoded &lt;i&gt;Grn&lt;\/i&gt; gene improves insulin resistance and glucose intolerance in obese mice fed a high-fat diet (HFD). However, it remains unclear which cells or organs are responsible for the beneficial metabolic effect of &lt;i&gt;Grn&lt;\/i&gt; depletion.Methods: Considering the critical role of macrophages in HFD-induced obesity and inflammation, we generated mice with a macrophage-specific &lt;i&gt;Grn&lt;\/i&gt; depletion (&lt;i&gt;Grn&lt;\/i&gt;-M\u03a6KO mice) by mating lysozyme M (LysM)-Cre and &lt;i&gt;Grn&lt;\/i&gt;-floxed mice. Body weight, food intake, energy expenditure, and glucose and insulin tolerance were compared between &lt;i&gt;Grn&lt;\/i&gt;-M\u03a6KO mice and their wildtype (WT) controls under normal chow diet (NCD)- or HFD-fed conditions. We also examined macrophage activation and inflammation- related gene expression in the visceral adipose tissue and hypothalamus along with insulin and leptin signaling.Results: &lt;i&gt;Grn&lt;\/i&gt;-M\u03a6KO mice showed no alteration in metabolic phenotypes under NCD-fed conditions. However, upon HFD feeding, these mice exhibited less weight gain and improved glucose and insulin tolerance compared to WT mice. Moreover, HFD-induced macrophage activation and proinflammatory cytokine expression were significantly reduced in both the adipose tissue and hypothalamus of &lt;i&gt;Grn&lt;\/i&gt;-M\u03a6KO mice, while HFD-induced impairments in leptin and insulin signaling showed improvement.Conclusion: Macrophage-derived PGRN and possibly other &lt;i&gt;Grn&lt;\/i&gt; products play a critical role in the development of HFD-induced obesity, tissue inflammation, and impaired hormonal signaling in both central and peripheral metabolic organs.<\/jats:p>","DOI":"10.4093\/dmj.2024.0486","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T04:13:56Z","timestamp":1741666436000},"page":"784-797","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Macrophage-Specific Progranulin Deficiency Prevents Diet-Induced Obesity through the Inhibition of Hypothalamic and Adipose Tissue Inflammation"],"prefix":"10.4093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8791-817X","authenticated-orcid":true,"given":"Chan Hee","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8384-617X","authenticated-orcid":true,"given":"Chae Beom","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Kyong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Hee","family":"Jang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se Hee","family":"Min","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Bum","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4881-0390","authenticated-orcid":true,"given":"Min-Seon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2567","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1172\/jci57132"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.90"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00379.2020"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1172\/jci29881"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1172\/jci19246"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1172\/jci59660"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1630"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.05.015"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.070"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1172\/jci88878"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-003-0474-3"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2014.04.003"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0812429"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.4808-14.2015"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1172\/jci34694"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(02)01141-8"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.12.002"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04518-2"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1221"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4495"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546108"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.m800019-jlr200"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.08.010"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1210\/me.2015-1232"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1147"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-020-00355-y"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1607-0"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091568"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt178"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2018.08.042"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00221.2013"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201502029"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab310"}],"container-title":["Diabetes &amp; Metabolism Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2024-0486.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2024.0486","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2024-0486.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T07:36:14Z","timestamp":1752219374000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2024.0486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7]]}},"URL":"https:\/\/doi.org\/10.4093\/dmj.2024.0486","relation":{},"ISSN":["2233-6079","2233-6087"],"issn-type":[{"value":"2233-6079","type":"print"},{"value":"2233-6087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"assertion":[{"value":"2024-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-11","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-01","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}