Serotonin signals through a gut-liver axis to regulate hepatic steatosis

Wonsuk Choi; Jun Namkung; Inseon Hwang; Hyeongseok Kim; Ajin Lim; Hye Jung Park; Hye Won Lee; Kwang Hyub Han; Seongyeol Park; Ji Seon Jeong; Geul Bang; Young Hwan Kim; Vijay K. Yadav; Gerard Karsenty; Young Seok Ju; Chan Choi; Jae Myoung Suh; Jun Yong Park; Sangkyu Park; Hail Kim

doi:10.1038/s41467-018-07287-7

Serotonin signals through a gut-liver axis to regulate hepatic steatosis

Wonsuk Choi, Jun Namkung, Inseon Hwang, Hyeongseok Kim, Ajin Lim, Hye Jung Park, Hye Won Lee, Kwang Hyub Han, Seongyeol Park, Ji Seon Jeong, Geul Bang, Young Hwan Kim, Vijay K. Yadav, Gerard Karsenty, Young Seok Ju, Chan Choi, Jae Myoung Suh, Jun Yong Park, Sangkyu Park, Hail Kim

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

87 Citations (Scopus)

Abstract

Nonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to HFD-induced hepatic steatosis, without affecting systemic energy homeostasis. Moreover, selective HTR2A antagonist treatment prevents HFD-induced hepatic steatosis. Thus, the gut TPH1-liver HTR2A axis shows promise as a drug target to ameliorate NAFLD with minimal systemic metabolic effects.

Original language	English
Article number	4824
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-07287-7
Publication status	Published - 2018 Dec 1

Bibliographical note

Publisher Copyright:
© 2018, The Author(s).

All Science Journal Classification (ASJC) codes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-018-07287-7

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Choi, W., Namkung, J., Hwang, I., Kim, H., Lim, A., Park, H. J., Lee, H. W., Han, K. H., Park, S., Jeong, J. S., Bang, G., Kim, Y. H., Yadav, V. K., Karsenty, G., Ju, Y. S., Choi, C., Suh, J. M., Park, J. Y., Park, S., & Kim, H. (2018). Serotonin signals through a gut-liver axis to regulate hepatic steatosis. Nature communications, 9(1), Article 4824. https://doi.org/10.1038/s41467-018-07287-7

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abstract = "Nonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to HFD-induced hepatic steatosis, without affecting systemic energy homeostasis. Moreover, selective HTR2A antagonist treatment prevents HFD-induced hepatic steatosis. Thus, the gut TPH1-liver HTR2A axis shows promise as a drug target to ameliorate NAFLD with minimal systemic metabolic effects.",

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Serotonin signals through a gut-liver axis to regulate hepatic steatosis

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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