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Among these, lipid-associated macrophages (LAMs) have emerged as an important subset that is frequently observed in cardiometabolically affected tissues. LAMs are defined by a transcriptional profile linked to lipid metabolism and processing. In parallel, the nuclear receptor liver X receptor (LXR) is a key transcription factor that regulates cholesterol efflux, fatty-acid synthesis, as well as inflammation pathways. Through these pathways, LXR agonism has been shown to limit atherosclerosis progression but also to promote hepatic steatosis. Beyond lipid metabolism, LXRs exert important immunoregulatory functions. In murine macrophages, LXR activation consistently dampens inflammatory responses. In contrast, human macrophages show more heterogeneous responses, with several studies indicating that LXRs can also promote pro-inflammatory gene programmes. These species-specific differences highlight a critical gap that currently limits the translation of preclinical findings. In this review, we integrate recent insights into LXRs in LAMs and cardiometabolic disease, emphasizing species-specific differences in macrophage LXR signalling between mice and humans. We discuss the contribution of LXR isoforms and emerging mechanisms by which LXRs influence inflammatory responses, and consider their implications for therapeutic targeting.<\/jats:p>","DOI":"10.1093\/cvr\/cvag214","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:37:44Z","timestamp":1791027464000},"source":"Crossref","is-referenced-by-count":0,"title":["Liver X receptor (LXR) signalling in macrophage inflammation and cardiometabolic disease"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9698-4046","authenticated-orcid":false,"given":"Lobke F","family":"Zijlstra","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Amsterdam UMC, Location University of Amsterdam , Meibergdreef 9, Amsterdam 1105AZ ,","place":["the Netherlands"]},{"name":"Amsterdam Cardiovascular Sciences, Atherosclerosis & Aortic Disease , Amsterdam, Meibergdreef 9, Amsterdam 1105AZ ,","place":["the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Disease , Amsterdam, Meibergdreef 9, Amsterdam 1105AZ ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno P J","family":"de Winther","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Amsterdam UMC, Location University of Amsterdam , Meibergdreef 9, Amsterdam 1105AZ ,","place":["the Netherlands"]},{"name":"Amsterdam Cardiovascular Sciences, Atherosclerosis & Aortic Disease , Amsterdam, Meibergdreef 9, Amsterdam 1105AZ ,","place":["the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Disease , Amsterdam, Meibergdreef 9, Amsterdam 1105AZ ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0014-5571","authenticated-orcid":false,"given":"Sander","family":"Kooijman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Leiden University Medical Center , Albinusdreef 2, Leiden 2333ZA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Castrillo","sequence":"additional","affiliation":[{"name":"Unidad de Biomedicina (Unidad Asociada al CSIC), Instituto Universitario de Investigaciones Biom\u00e9dicas y Sanitarias (IUIBS), Grupo de Investigaci\u00f3n Farmacolog\u00eda Molecular y Traslacional (BIOPharma), Universidad de Las Palmas de Gran Canaria , Las Palmas ,","place":["Spain"]},{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols-Morreale, Centro Mixto CSIC-Universidad Aut\u00f3noma de Madrid , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9029-3991","authenticated-orcid":false,"given":"Annette E","family":"Neele","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Amsterdam UMC, Location University 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