Clusterin/ApoJ enhances central leptin signaling through Lrp2‐mediated endocytosis |
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| Authors: | Kyunghee Byun So Young Gil Churl Namkoong Byung‐Soo Youn Hu Huang Mi‐Seon Shin Gil Myoung Kang Hyun‐Kyong Kim Bonghee Lee Young‐Bum Kim Min‐Seon Kim |
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| Institution: | 1. Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, , Incheon, Korea;2. Asan Institute for Life Sciences, University of Ulsan College of Medicine, , Seoul, Korea;3. Department of Anatomy, Wonkwang University School of Medicine, , Iksan, Korea;4. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, , Boston, MA, USA;5. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, , Seoul, Korea |
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| Abstract: | 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. |
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| Keywords: | clusterin endocytosis leptin Lrp2 Stat3 |
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