{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T06:01:15Z","timestamp":1785218475057,"version":"3.55.0"},"reference-count":32,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Clozapine, an atypical antipsychotic, is effective for treatment-resistant schizophrenia but frequently causes metabolic adverse effects, including hepatic lipid accumu-lation, inflammation and insulin resistance. Adiponectin, an adipocyte-derived cytokine with anti-inflammatory and insulin-sensitizing properties, may counteract these effects; however, its ability to mitigate clozapine-induced hepatic alterations remains unclear. This study examined whether adiponectin overexpression reduces clozapine-induced lipid accumulation, inflammatory signaling, and whether it restores insulin-related Akt signaling in human HepG2 liver cells. Cells were treated with 25\u202f\u03bcM clozapine for 24 or 48\u202fh, and adiponectin was overexpressed by plasmid transfection. Lipid accumulation was quantified by BODIPY staining. AdipoR1 and AdipoR2 expression was analyzed by qPCR, and protein levels of FASN, phosphorylated NF-\u03baB, and phosphorylated Akt were assessed by Western blotting. Clozapine increased lipid accumulation, upregulated FASN, and reduced AdipoR1 and AdipoR2 expression. Adiponectin overexpression significantly decreased lipid levels, which was associated with reduced NF-\u03baB phosphorylation, suggesting attenuation of inflammatory signaling. However, adiponectin did not restore insulin-stimulated Akt phosphorylation. In summary, adiponectin selectively reduced clozapine-induced lipid accumulation and inflammatory signaling in HepG2 cells, whereas impaired insulin-stimulated Akt phosphorylation remained unchanged under the present experimental conditions. These findings indicate a selective protective role of adiponectin and suggest its potential as a modulator of clozapine-induced metabolic side effects.<\/jats:p>","DOI":"10.1515\/biol-2025-1333","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T10:03:33Z","timestamp":1784282613000},"source":"Crossref","is-referenced-by-count":0,"title":["Adiponectin improves clozapine-induced lipid accumulation and inflammation without affecting insulin resistance"],"prefix":"10.1515","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4852-7214","authenticated-orcid":false,"given":"I-Lun","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Bioscience and Biotechnology , National Taiwan Ocean University , Keelung , 202301 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-5937","authenticated-orcid":false,"given":"Shih-Chao","family":"Lin","sequence":"additional","affiliation":[{"name":"Bachelor Program in Marine Biotechnology , National Taiwan Ocean University , Keelung , 202301 , Taiwan"},{"name":"Marine Biotechnology and Environmental Ecology Sustainability Department , National Taiwan Ocean University , Keelung , 202301 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology , National Taiwan Ocean University , Keelung , 202301 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Shan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Bachelor Program in Marine Biotechnology , National Taiwan Ocean University , Keelung , 202301 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-4697","authenticated-orcid":false,"given":"Shiow-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology , National Taiwan Ocean University , Keelung , 202301 , Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"2026072805573180538_j_biol-2025-1333_ref_001","doi-asserted-by":"crossref","unstructured":"Rahman, T, Lauriello, J. 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