Clusterin/ApoJ enhances central leptin signaling through Lrp2‐mediated endocytosis. (13th May 2014)

• Record Type: Journal Article
• Authors: Byun, Kyunghee; Gil, So Young; Namkoong, Churl; Youn, Byung‐Soo; Huang, Hu; Shin, Mi‐Seon; Kang, Gil Myoung; Kim, Hyun‐Kyong; Lee, Bonghee; Kim, Young‐Bum; Kim, Min‐Seon
• Is Part Of: EMBO reports. Volume 15:Number 7(2014:Jul.)
• Page Start: 801
• Page End: 808
• Publication Date: 2014-05-13
• Subjects: Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201338317
• Languages: English
• ISSNs: 1469-221X

Abstract

<abstract abstract-type="main" id="embr201338317-abs-0001"> <title>Abstract</title> <p>Hypothalamic leptin signaling plays a central role in maintaining body weight homeostasis. Here, we show that clusterin/ApoJ, recently identified as an anorexigenic neuropeptide, is an important regulator in the hypothalamic leptin signaling pathway. Coadministration of clusterin potentiates the anorexigenic effect of leptin and boosts leptin‐induced hypothalamic Stat3 activation. In cultured neurons, clusterin enhances receptor binding and subsequent endocytosis of leptin. These effects are mainly mediated through the LDL receptor‐related protein‐2 (Lrp2). Notably, inhibition of hypothalamic clusterin, Lrp2 or endocytosis abrogates anorexia and hypothalamic Stat3 activation caused by leptin. These findings propose a novel regulatory mechanism in central leptin signaling pathways.</p> </abstract>