{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:13:53Z","timestamp":1790648033542,"version":"4.1.0"},"posted":{"date-parts":[[2026,1,16]]},"group-title":"Neuroscience","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["26POST1562706"],"award-info":[{"award-number":["26POST1562706"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Microglia play essential roles in maintaining energy homeostasis, and their dysfunction contributes to metabolic disease. Although high-fat diet (HFD) exposure induces microglial activation, the underlying mechanisms remain poorly defined. Here, we identified a previously unrecognized role for THIK-1 channel in mediating glucose sensing of microglia in arcuate nucleus of the hypothalamus (ARH), during HFD-induced obesity. Pharmacological inhibition of THIK-1 channel with tetrapentylammonium (TPA) suppresses feeding and attenuates body-weight gain in diet induced obese mice. Mechanistically, inhibition of agouti-related peptide (AgRP) neurons is indispensable for TPA-induced hypophagia. Moreover, THIK-1 inhibition promotes microglial phagocytosis of perineuronal nets (PNNs), leading to reduced AgRP neuronal activity and feeding suppression. Together, these findings establish THIK-1 as a critical glucose sensor in hypothalamic microglia and uncover a microglia-dependent pathway through which overnutrition modulates AgRP neuronal activity via PNN remodeling to regulate energy balance, highlighting THIK-1 as a potential therapeutic target for treatment of diet-induced obesity.<\/jats:p>","DOI":"10.64898\/2026.01.15.699765","type":"posted-content","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:30:18Z","timestamp":1768609818000},"source":"Crossref","is-referenced-by-count":1,"title":["THIK-1 channel mediates microglial glucose sensing and modulates AgRP neurons"],"prefix":"10.64898","author":[{"given":"Qingzhuo","family":"Liu","sequence":"first","affiliation":[{"name":"Center for Molecular Psychiatry, Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Tampa, FL, 33613, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan 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