{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:10:00Z","timestamp":1773195000566,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Adipocyte Fatty Acid-Binding Protein 4 (FABP4) exerts a direct negative inotropic effect on cardiac muscle, but the underlying cellular mechanisms remain elusive. This study aimed to dissect the specific effects of FABP4 on the contractility and calcium (Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ) homeostasis of isolated mouse ventricular myocytes and to characterize the functional role and critical residues of its N-terminal domain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Contractility and intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      transients were simultaneously measured in isolated adult mouse ventricular myocytes using an IonOptix system following acute application of recombinant human FABP4 or its synthetic N-terminal peptide (FABP4\n                      <jats:sub>aa1-20<\/jats:sub>\n                      ). L-type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      current was assessed via the whole-cell patch-clamp technique. Dose-response curves were analyzed using non-linear regression, and site-directed mutagenesis (E15K) was performed to evaluate the functional importance of a key amino acid residue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FABP4 inhibited myocyte contraction in a biphasic, dose-dependent manner, with a high-affinity (EC\n                      <jats:sub>50<\/jats:sub>\n                      = 0.010 pM) and a low-affinity (EC\n                      <jats:sub>50<\/jats:sub>\n                      = 0.120 nM) component. This inhibition was largely independent of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      handling, as Ca\n                      <jats:sup>2+<\/jats:sup>\n                      transient amplitude was only weakly attenuated at higher concentrations (EC\n                      <jats:sub>50<\/jats:sub>\n                      = 0.412 nM), and L-type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      current was unaffected. In stark contrast, the FABP4\n                      <jats:sub>aa1-20<\/jats:sub>\n                      peptide also inhibited contraction (EC\n                      <jats:sub>50<\/jats:sub>\n                      = 0.110 nM) but did so via a Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -dependent pathway, robustly suppressing Ca\n                      <jats:sup>2+<\/jats:sup>\n                      transients. Mutation of glutamic acid at position 15 (E15K) significantly attenuated the peptide\u2019s inhibitory activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Full-length FABP4 suppresses cardiomyocyte contractility primarily through a Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -independent pathway, likely by reducing myofilament Ca\n                      <jats:sup>2+<\/jats:sup>\n                      sensitivity. Conversely, its isolated N-terminal domain operates via a distinct, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -dependent mechanism. These findings reveal a complex dual-pathway regulation of cardiac function by FABP4 and identify its N-terminal region as a potential therapeutic target for mitigating obesity-related cardiac dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1682010","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:30:24Z","timestamp":1773120624000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipocyte fatty acid-binding protein 4 suppresses contraction of mouse ventricular myocytes via a calcium-independent pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Cuihua","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiac Rehabilitation, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daofeng","family":"You","sequence":"additional","affiliation":[{"name":"Emergency Department, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Arrhythmia Center, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cardiac Rehabilitation, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenghong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Rehabilitation, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Research Institute, Jiangxi Provincial People\u2019s Hospital","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Arrhythmia Center, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"T47","DOI":"10.1530\/JOE-13-0339","article-title":"Adipocytokines in obesity and metabolic disease","volume":"220","author":"Cao","year":"2014","journal-title":"J. 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