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We herein characterised SARS\u2010CoV\u20102 entry points in visceral (VAT) and subcutaneous (SAT) adipose tissue from people with obesity and determined whether the adipo\u2010myokines FNDC4 and FNDC5 modulate SARS\u2010CoV\u20102 spike glycoprotein subunit 1 (S1)\u2013induced inflammation in adipocytes and macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Plasma concentrations of FNDC4, FNDC5 and angiotensin\u2010converting enzyme 2 (ACE2) were measured in 183 participants with obesity and normal weight. Expression of SARS\u2010CoV\u20102 host cell entry receptors was analysed in paired VAT and SAT biopsies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009121). The effects of FNDC4 and FNDC5 on S1\u2010induced inflammatory responses were evaluated in\u00a0vitro using human visceral adipocytes and THP\u20101\u2010derived macrophages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Obesity was associated with higher circulating ACE2 and increased expression of SARS\u2010CoV\u20102 entry receptors (ACE2, CD147, DPP4 and neuropilin\u20101) in VAT, whereas plasma FNDC4 and FNDC5 levels were reduced. FNDC4, FNDC5 and ACE2 co\u2010localised with macrophage populations in VAT, and\n                      <jats:italic>FNDC4<\/jats:italic>\n                      and\n                      <jats:italic>FNDC5<\/jats:italic>\n                      transcripts positively correlated with genes involved in viral entry and priming. Both adipo\u2010myokines attenuated S1\u2010induced M1 macrophage polarisation and HMGB1 secretion and reduced HMGB1 expression in adipocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Reduced FNDC4 and FNDC5 levels in obesity may amplify SARS\u2010CoV\u20102 S1\u2010induced inflammatory responses in VAT macrophages and adipocytes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70215","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:21:20Z","timestamp":1777375280000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FNDC4 and FNDC5 Attenuate SARS\u2010CoV\u20102 S1\u2010Induced Inflammatory Responses in Human Adipose 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