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However, the precise molecular mechanisms by which tanycytes modulate lipid utilization remain unclear. Here, we report that the catalytic subunit of protein phosphatase 2\u2009A (PP2Ac), a serine\/threonine phosphatase, is expressed in tanycytes and its accumulation and activation occur in response to high-fat diet consumption.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    , tanycytic PP2Ac responds to palmitic acid (PA) exposure and accumulates and is activated at an early stage in an AMPK-dependent manner. Furthermore, activated PP2Ac boosts hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) accumulation, resulting in upregulation of an array of cytokines. Pretreatment with a PP2Ac inhibitor, LB100, prevented the PA-induced elevation of vascular endothelial growth factor (VEGF), fibroblast growth factor 1 (FGF1), hepatocyte growth factor (HGF), and dipeptidyl peptidase IV (DPPIV or CD26). Our results disclose a mechanism of lipid metabolism in tanycytes that involves the activation of PP2Ac and highlight the physiological significance of PP2Ac in hypothalamic tanycytes in response to overnutrition and efficacious treatment of obesity.\n                  <\/jats:p>","DOI":"10.1177\/0271678x231219115","type":"journal-article","created":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T09:48:45Z","timestamp":1702115325000},"page":"985-999","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Saturated fatty acids stimulate cytokine production in tanycytes via the PP2Ac-dependent signaling pathway"],"prefix":"10.1177","volume":"44","author":[{"given":"Danyang","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Brain Science and Brain Medicine, Hangzhou, China"},{"name":"Nanhu Brain-computer Interface Institute, Hangzhou 311100, China"},{"name":"Department of Ophthalmology of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Zhejiang Laboratory for Systems &amp; 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