{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:05:16Z","timestamp":1790247916446,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The patatin\u2010like phospholipase domain\u2010containing protein 3 (Pnpla3) I148M polymorphism is a well\u2010established genetic determinant of metabolic dysfunction\u2010associated steatotic liver disease (MASLD), and emerging evidence links it to chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the mechanisms underlying this relationship remain unclear. The goal of this study was to investigate the role of the Pnpla3\n                    <jats:sup>I148M<\/jats:sup>\n                    polymorphism on kidney function, blood pressure, and cardiac function in a mouse model carrying the identical human polymorphism. Male and female Pnpla3\n                    <jats:sup>I148M<\/jats:sup>\n                    knock\u2010in and control C57BL\/6 mice were fed either a normal sucrose diet (NSD) or a high sucrose diet (HSD) for 8\u2009weeks. Glomerular filtration rate (GFR), blood pressure, cardiac, and vascular function were measured in each group. Renal cortical protein expression and kinome profiles were analyzed to identify pathways associated with hyperfiltration and renal injury. Pnpla3\n                    <jats:sup>I148M<\/jats:sup>\n                    mice exhibited increased renal sodium transporter levels and hyperfiltration, which was compounded by albuminuria in HSD mice. Pnpla3\n                    <jats:sup>I148M<\/jats:sup>\n                    mice were also hypertensive and exhibited impaired systolic function, consistent with pressure\u2010overload\u2010induced cardiac remodeling. Renal kinome profiling revealed sex\u2010 and diet\u2010dependent alterations in serine\/threonine kinases, primarily involving isoforms of protein kinase C (PKC), protein kinase A (PKA), cGMP\u2010dependent protein kinase (PRKG), and calcium\/calmodulin\u2010dependent protein kinase (CaMK). Our findings suggest that Pnpla3\n                    <jats:sup>I148M<\/jats:sup>\n                    acts as a systemic cardio\u2010renal risk allele that links metabolic dysregulation to progressive end\u2010organ damage via renal kinase remodeling in a sex\u2010 and diet\u2010dependent manner.\n                  <\/jats:p>","DOI":"10.1096\/fba.2026-00222","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:43:52Z","timestamp":1789807432000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Human\n                    <scp>\n                      PNPLA3\n                      <sup>I148M<\/sup>\n                    <\/scp>\n                    Polymorphism Alters the Renal Kinome\n                    <scp>and Transporters<\/scp>\n                    to Cause Hyperfiltration and Hypertension"],"prefix":"10.1096","volume":"8","author":[{"given":"Gertrude","family":"Arthur","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Biophysics, Cardiorenal, and Metabolic Diseases Research Center University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael I.","family":"Adenawoola","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics, Cardiorenal, and Metabolic Diseases Research Center University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Wahba","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics, Cardiorenal, and Metabolic Diseases Research Center University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bentley 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