The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT–liver communication

Carlos H. Sponton, Takashi Hosono, Junki Taura, Mark P. Jedrychowski, Takeshi Yoneshiro, Qiang Wang, Makoto Takahashi, Yumi Matsui, Kenji Ikeda, Yasuo Oguri, Kazuki Tajima, Kosaku Shinoda, Rachana N. Pradhan, Yong Chen, Zachary Brown, Lindsay S. Roberts, Carl C. Ward, Hiroki Taoka, Yoko Yokoyama, Mitsuhiro WatanabeHiroshi Karasawa, Daniel K. Nomura, Shingo Kajimura

Research output: Contribution to journalArticle

Abstract

While brown adipose tissue (BAT) is well-recognized for its ability to dissipate energy in the form of heat, recent studies suggest multifaced roles of BAT in the regulation of glucose and lipid homeostasis beyond stimulating thermogenesis. One of the functions involves interorgan communication with metabolic organs, such as the liver, through BAT-derived secretory factors, a.k.a., batokine. However, the identity and the roles of such mediators remain insufficiently understood. Here, we employed proteomics and transcriptomics in human thermogenic adipocytes and identified previously unappreciated batokines, including phospholipid transfer protein (PLTP). We found that increased circulating levels of PLTP, via systemic or BAT-specific overexpression, significantly improve glucose tolerance and insulin sensitivity, increased energy expenditure, and decrease the circulating levels of cholesterol, phospholipids, and sphingolipids. Such changes were accompanied by increased bile acids in the circulation, which in turn enhances glucose uptake and thermogenesis in BAT. Our data suggest that PLTP is a batokine that contributes to the regulation of systemic glucose and lipid homeostasis as a mediator of BAT-liver interorgan communication.

Original languageEnglish (US)
Article numbere49828
JournalEMBO Reports
Volume21
Issue number9
DOIs
StatePublished - Sep 3 2020

Keywords

  • brown adipose tissue
  • interorgan communication
  • lipid homeostasis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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    Sponton, C. H., Hosono, T., Taura, J., Jedrychowski, M. P., Yoneshiro, T., Wang, Q., Takahashi, M., Matsui, Y., Ikeda, K., Oguri, Y., Tajima, K., Shinoda, K., Pradhan, R. N., Chen, Y., Brown, Z., Roberts, L. S., Ward, C. C., Taoka, H., Yokoyama, Y., ... Kajimura, S. (2020). The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT–liver communication. EMBO Reports, 21(9), [e49828]. https://doi.org/10.15252/embr.201949828