{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T20:12:50Z","timestamp":1785269570808,"version":"3.55.0"},"reference-count":69,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Elevated circulating lipids are linked to cardiovascular disease (\n                      <jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content>\n                      ), especially in insulin\u2010resistant states like polycystic ovary syndrome (\n                      <jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>\n                      ), but their effects on cardiovascular risk proteins (\n                      <jats:styled-content style=\"fixed-case\">CVRPs<\/jats:styled-content>\n                      ) remain unclear. This study used a two\u2010step approach to examine acute cardiovascular proteomic responses to lipid\u2010induced metabolic stress. We first identified proteins altered by lipids and insulin in healthy control (\n                      <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>\n                      ) women, then assessed whether these responses were similar or divergent in women with\n                      <jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a randomised cross\u2010over study, 10 healthy controls and 12 women with\n                      <jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>\n                      underwent 5\u2010h saline (control) or intralipid infusions. After 3\u2009h, a 2\u2010h hyperinsulinemic\u2010euglycemic clamp was initiated. Plasma\n                      <jats:styled-content style=\"fixed-case\">CVRP<\/jats:styled-content>\n                      expression was assessed at baseline, post\u2010lipid (180\u2009min) and post\u2010clamp (300\u2009min) using\n                      <jats:styled-content style=\"fixed-case\">SOMAscan<\/jats:styled-content>\n                      proteomics.\n                      <jats:styled-content style=\"fixed-case\">STRING<\/jats:styled-content>\n                      and pathway enrichment analyses were performed to explore functional associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the\n                      <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>\n                      group, lipid infusion altered the expression of 11 out of 54\n                      <jats:styled-content style=\"fixed-case\">CVRPs<\/jats:styled-content>\n                      including increases in\n                      <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">IL2RA<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">TACI<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">SLAF5<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">DCN<\/jats:styled-content>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05) and decreases in\n                      <jats:styled-content style=\"fixed-case\">THPO<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">BOC<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">SOD2<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">FGF23<\/jats:styled-content>\n                      , and\n                      <jats:styled-content style=\"fixed-case\">AgRP<\/jats:styled-content>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05). Most changes reversed with insulin, but\n                      <jats:styled-content style=\"fixed-case\">BOC<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">SOD2<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">MMP12<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">FGF23<\/jats:styled-content>\n                      , and\n                      <jats:styled-content style=\"fixed-case\">DCN<\/jats:styled-content>\n                      remained dysregulated. In\n                      <jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>\n                      , responses mirrored the\n                      <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>\n                      group except for lower\n                      <jats:styled-content style=\"fixed-case\">AgRP<\/jats:styled-content>\n                      following lipid infusion (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.01), and persistent elevation of\n                      <jats:styled-content style=\"fixed-case\">SLAF5<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">DCN<\/jats:styled-content>\n                      following insulin (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05). Enrichment analysis linked altered proteins to immune activation, cell proliferation, and cytokine\u2010receptor signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Acute lipid infusion revealed shared and phenotype\u2010specific proteomic responses linked to early vascular stress. In\n                      <jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>\n                      , persistent dysregulation suggests reduced metabolic adaptability, with exploratory signals that may complement established biomarkers of early cardiovascular risk.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70154","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T09:14:38Z","timestamp":1759137278000},"page":"7464-7475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Shared and divergent acute cardiovascular risk protein responses to lipid infusion in women with and without\n                    <scp>PCOS<\/scp>"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0085-5338","authenticated-orcid":false,"given":"Ebrahim","family":"Rajab","sequence":"first","affiliation":[{"name":"School of 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