{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T22:04:41Z","timestamp":1764540281377,"version":"3.37.3"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T00:00:00Z","timestamp":1595635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81000581","81471358","81771450"],"award-info":[{"award-number":["81000581","81471358","81771450"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Science and Technology Commission Foundation","award":["14411969000"],"award-info":[{"award-number":["14411969000"]}]},{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","award":["20152530"],"award-info":[{"award-number":["20152530"]}],"id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008410","name":"Shanghai Municipal Population and Family Planning Commission","doi-asserted-by":"publisher","award":["201540029"],"award-info":[{"award-number":["201540029"]}],"id":[{"id":"10.13039\/501100008410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Accompanied with profound efficacy, atypical antipsychotics (AAPs) contribute to metabolic adverse effects with few effective strategies to attenuate. Serotonin 5-HT2C receptor (HTR2C) plays a critical role in hyperphagia and weight gain induced by AAPs, and expression of phosphatase tensin homolog (PTEN) in the hypothalamus also affects feeding behavior and weight change. Moreover, PTEN has a physical crosstalk between PTEN and a region in the third intracellular loop (3L4F) of the HTR2C. Tat-3L4F has the property to disrupt crosstalk between PTEN and HTR2C. This is the first study to our knowledge to investigate the effect of Tat-3L4F on olanzapine-induced metabolic abnormalities and PTEN\/ phosphatidylinositol 3-kinase\/protein kinase B expression in the hypothalamus in rats.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The effects of Tat-3L4F were investigated through measuring body weight, food intake, and blood glucose. In addition, PTEN\/phosphatidylinositol 3-kinase\/protein kinase B level in the hypothalamus was detected by immunofluorescence assay and western blot. Metabolites in the liver tissue were detected by liquid chromatography-mass spectrometry and analyzed by multivariate analyses and pairwise comparison.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our results showed that hyperphagia and weight gain were evident in the olanzapine alone\u2013fed rats but was attenuated after Tat-3L4F treatment. In addition, oral glucose tolerance test indicated blood glucose at 120 minutes was higher in the olanzapine alone\u2013treated group than in groups treated with vehicle and olanzapine\u2009+\u2009Tat-3L4F (10 \u03bcmol kg\u22121 per day). Furthermore, compared with olanzapine alone treatment, treatment with Tat-3L4F (10 \u03bcmol kg\u22121 per day) significantly inhibited PTEN expression in the hypothalamus. The olanzapine alone\u2013treated group had the highest bile acid level, followed by the olanzapine with Tat-3L4F (1 \u03bcmol kg\u22121) group, olanzapine with Tat-3L4F (10 \u03bcmol kg\u22121) group, and vehicle group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our present results reveal that Tat-3L4F is a potential pharmacological strategy for suppressing hyperphagia and weight gain induced by olanzapine, which acts through disrupting crosstalk between HTR2C and PTEN as a result of PTEN downregulation in the hypothalamus.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyaa001","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T12:10:33Z","timestamp":1579090233000},"page":"481-490","source":"Crossref","is-referenced-by-count":8,"title":["A Novel Synthetic Interfering Peptide Tat-3L4F Attenuates Olanzapine-Induced Weight Gain Through Disrupting Crosstalk Between Serotonin Receptor 2C and Protein Phosphatase and Tensin Homolog in Rats"],"prefix":"10.1093","volume":"23","author":[{"given":"Yewei","family":"Wang","sequence":"first","affiliation":[{"name":"Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China"},{"name":"Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China"},{"name":"Innovative Research Team of High-level Local Universities in Shanghai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[{"name":"Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China"},{"name":"Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China"},{"name":"Innovative Research Team of High-level Local Universities in 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