{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:08:01Z","timestamp":1789409281270,"version":"build-2803163510"},"reference-count":57,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,7,1]]},"abstract":"<jats:p>Nonalcoholic steatohepatitis (NASH) is commonly found in patients with obesity and is often accompanied with abnormally elevated levels of plasma leptin, i.e. hyperleptinemia. A relatively high population of NASH patients develops hepatic fibrosis, even cirrhosis. Hepatic stellate cells (HSCs) are the major effector cells during liver fibrogenesis and could be activated by leptin. The antioxidant curcumin, a phytochemical from turmeric, has been shown to suppress HSC activation in vitro and in vivo. This project is to evaluate the effect of curcumin on leptin-induced HSC activation and to elucidate the underlying mechanisms. We hypothesize that curcumin abrogates the stimulatory effect of leptin on HSC activation by interrupting leptin signaling and attenuating leptin-induced oxidative stress. Curcumin eliminates the stimulatory effects of leptin on regulating expression of genes closely relevant to HSC activation. Curcumin interrupts leptin signaling by reducing phosphorylation levels of leptin receptor (Ob-R) and its downstream intermediators. In addition, curcumin suppresses gene expression of Ob-R in HSCs, which requires the activation of endogenous peroxisome proliferator-activated receptor-\u03b3 and de novo synthesis of glutathione. In conclusion, our results demonstrate that curcumin abrogates the stimulatory effect of leptin on HSC activation in vitro by reducing the phosphorylation level of Ob-R, stimulating peroxisome proliferator-activated receptor-\u03b3 activity, and attenuating oxidative stress, leading to the suppression of Ob-R gene expression and interruption of leptin signaling. These results provide novel insights into therapeutic mechanisms of curcumin in inhibiting HSC activation and intervening liver fibrogenesis associated with hyperleptinemia in NASH patients.<\/jats:p>","DOI":"10.1210\/en.2008-1601","type":"journal-article","created":{"date-parts":[[2009,3,20]],"date-time":"2009-03-20T00:33:24Z","timestamp":1237509204000},"page":"3011-3020","source":"Crossref","is-referenced-by-count":79,"title":["Curcumin Eliminates Leptin\u2019s Effects on Hepatic Stellate Cell Activation via Interrupting Leptin Signaling"],"prefix":"10.1210","volume":"150","author":[{"given":"Youcai","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Pathology (Y.T., S.Z., A.C.), School of Medicine, Saint Louis University, St. Louis, Missouri 63104"},{"name":"Department of Pediatrics (Y.T.), The Third Affiliated Hospital, Zhengzhou University, Henan 450001, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizhong","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Pathology (Y.T., S.Z., A.C.), School of Medicine, Saint Louis University, St. Louis, Missouri 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anping","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology (Y.T., S.Z., A.C.), School of Medicine, Saint Louis University, St. Louis, Missouri 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2009,3,19]]},"reference":[{"key":"2020071612371515100_R1","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1053\/gast.2002.36572","article-title":"AGA technical review on nonalcoholic fatty liver 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