{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:09:45Z","timestamp":1779196185197,"version":"3.51.4"},"reference-count":24,"publisher":"American Society for Clinical Investigation","issue":"17","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01-DK048419"],"award-info":[{"award-number":["R01-DK048419"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["P30-DK34933"],"award-info":[{"award-number":["P30-DK34933"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,5]]},"abstract":"<jats:p>\n                    Research shows that rats and humans on a high-fat diet (HFD) are less sensitive to satiety signals known to act via vagal afferent pathways. We hypothesize that HFD causes an upregulation of 2-pore domain potassium channels, resulting in hyperpolarization of nodose ganglia (NG) and decreased vagal response to satiety signals, which contribute to hyperphagia. We show that a 2-week HFD caused an upregulation of 2-pore domain TWIK-related spinal cord K\n                    <jats:sup>+<\/jats:sup>\n                    (TRESK) and TWIK-related acid-sensitive K\n                    <jats:sup>+<\/jats:sup>\n                    1 (TASK1) channels by 330% \u00b1 50% and 60% \u00b1 20%, respectively, in NG. Patch-clamp studies of isolated NG neurons demonstrated a decrease in excitability. In vivo single-unit NG recordings showed that a 2-week HFD led to a 55% reduction in firing frequency in response to CCK-8 or leptin stimulation. NG electroporation with TRESK siRNA restored NG responsiveness to CCK-8 and leptin. Rats fed a 2-week HFD consumed ~40% more calories compared with controls. Silencing NG TRESK but not TASK1 channel expression in HFD-fed rats restored normal calorie consumption. In conclusion, HFD caused upregulation of TRESK channels, resulting in NG hyperpolarization and decreased vagal responsiveness to satiety signals. This finding provides a pharmacological target to prevent or treat HFD-induced hyperphagia.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.130402","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T11:01:02Z","timestamp":1567594862000},"source":"Crossref","is-referenced-by-count":10,"title":["High-fat diet\u2013induced vagal afferent dysfunction via upregulation of 2-pore domain potassium TRESK 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