Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway

So Young Gil, Byung Soo Youn, Kyunghee Byun, Hu Huang, Churl Namkoong, Pil Geum Jang, Joo Yong Lee, Young Hwan Jo, Gil Myoung Kang, Hyun Kyong Kim, Mi Seon Shin, Claus U. Pietrzik, Bonghee Lee, Young Bum Kim, Min Seon Kim

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Hypothalamic feeding circuits are essential for the maintenance of energy balance. There have been intensive efforts to discover new biological molecules involved in these pathways. Here we report that central administration of clusterin, also called apolipoprotein J, causes anorexia, weight loss and activation of hypothalamic signal transduction-activated transcript-3 in mice. In contrast, inhibition of hypothalamic clusterin action results in increased food intake and body weight, leading to adiposity. These effects are likely mediated through the mutual actions of the low-density lipoprotein receptor-related protein-2, a potential receptor for clusterin, and the long-form leptin receptor. In response to clusterin, the low-density lipoprotein receptor-related protein-2 binding to long-form leptin receptor is greatly enhanced in cultured neuronal cells. Furthermore, long-form leptin receptor deficiency or hypothalamic low-density lipoprotein receptor-related protein-2 suppression in mice leads to impaired hypothalamic clusterin signalling and actions. Our study identifies the hypothalamic clusterin-low-density lipoprotein receptor-related protein-2 axis as a novel anorexigenic signalling pathway that is tightly coupled with long-form leptin receptor-mediated signalling.

Original languageEnglish (US)
Article number1862
JournalNature communications
Volume4
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Gil, S. Y., Youn, B. S., Byun, K., Huang, H., Namkoong, C., Jang, P. G., Lee, J. Y., Jo, Y. H., Kang, G. M., Kim, H. K., Shin, M. S., Pietrzik, C. U., Lee, B., Kim, Y. B., & Kim, M. S. (2013). Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway. Nature communications, 4, [1862]. https://doi.org/10.1038/ncomms2896