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However, the metabolic cues that drive Treg subset specialization in the obese VAT niche remain elusive. Here, we demonstrated that palmitic acid (PA) instigated chronic VAT inflammation and systemic metabolic disturbance by compromising the immunosuppressive function of the ICOS\n                    <jats:sup>hi<\/jats:sup>\n                    Treg subset. PA, but not oleic acid, activated CREB\/ATF bZIP transcription factor (\n                    <jats:italic>Crebzf<\/jats:italic>\n                    ) expression in VAT Tregs from high-fat, high-sucrose diet\u2013induced (HFHS diet\u2013induced) obese and ob\/ob mice.\n                    <jats:italic>Crebzf<\/jats:italic>\n                    deficiency significantly attenuated diet-induced obesity and inflammation by upregulating the suppressive function of VAT ICOS\n                    <jats:sup>hi<\/jats:sup>\n                    Tregs. Moreover, adoptive transfer of\n                    <jats:italic>Crebzf<\/jats:italic>\n                    -deficient ICOS\n                    <jats:sup>hi<\/jats:sup>\n                    Tregs into\n                    <jats:italic>Rag<\/jats:italic>\n                    1\n                    <jats:italic>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice alleviated HFHS diet\u2013induced inflammation and metabolic disorders more effectively than transfer of\n                    <jats:italic>Crebzf<\/jats:italic>\n                    -sufficient ICOS\n                    <jats:sup>hi<\/jats:sup>\n                    Tregs. Mechanistically, CREBZF interacted with c-JUN to inhibit\n                    <jats:italic>Foxp3<\/jats:italic>\n                    activity, thereby impairing the stability and inhibitory cytokine production of ICOS\n                    <jats:sup>hi<\/jats:sup>\n                    Tregs. In humans,\n                    <jats:italic>CREBZF<\/jats:italic>\n                    levels in VAT Tregs were elevated and negatively correlated with\n                    <jats:italic>FOXP3<\/jats:italic>\n                    activity. Collectively, these findings uncover a specific ICOS\n                    <jats:sup>hi<\/jats:sup>\n                    Treg subset that responds to PA, thereby coupling obesogenic signals to VAT remodeling and systemic metabolic homeostasis.\n                  <\/jats:p>","DOI":"10.1172\/jci207089","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:00:33Z","timestamp":1784822433000},"source":"Crossref","is-referenced-by-count":1,"title":["Palmitic acid coordinates impaired visceral adipose ICOShi Treg-mediated immunosuppression and systemic metabolic disturbance during obesity"],"prefix":"10.1172","volume":"136","author":[{"given":"Weitong","family":"Su","sequence":"first","affiliation":[{"name":"Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 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