5 :: KDA, Korean Diabetes Association ::
Subject    :    [2018 Jun;42(3)] Inhibition of Serotonin Synthesis Induces Negative Hepatic Lipid Balance
Writer KDA
Date 2019-03-06 09:46:39 Hit 480
Diabetes Metab J. 2018 Jun;42(3):233-243. English.
Published online Apr 25, 2018.  https://doi.org/10.4093/dmj.2017.0084 
Copyright © 2018 Korean Diabetes Association
   
Inhibition of Serotonin Synthesis Induces Negative Hepatic Lipid Balance
Jun Namkung,1,2 Ko Eun Shong,1,3 Hyeongseok Kim,1 Chang-Myung Oh,1 Sangkyu Park,1,4 and Hail Kim1,3
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
2Department of Biochemistry, Yonsei University Wonju College of Medicine, Wonju, Korea.
3Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
4Department of Biochemistry, Catholic Kwandong University College of Medicine, Gangneung, Korea.

Corresponding authors: Sangkyu Park. Department of Biochemistry, Catholic Kwandong University College of Medicine, 24 Beomil-ro 579beon-gil, Gangneung 25601, Korea. Email: 49park@cku.ac.kr Corresponding authors: Hail Kim. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea. Email: hailkim@kaist.edu 
 
Received November 29, 2017; Accepted February 14, 2018.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.



Abstract

Background

Hepatic steatosis is caused by metabolic stress associated with a positive lipid balance, such as insulin resistance and obesity. Previously we have shown the anti-obesity effects of inhibiting serotonin synthesis, which eventually improved insulin sensitivity and hepatic steatosis. However, it is not clear whether serotonin has direct effect on hepatic lipid accumulation. Here, we showed the possibility of direct action of serotonin on hepatic steatosis.

Methods

Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 to inhibit serotonin synthesis and fed with high fat diet (HFD) or high carbohydrate diet (HCD) to induce hepatic steatosis. Hepatic triglyceride content and gene expression profiles were analyzed.

Results

Pharmacological and genetic inhibition of serotonin synthesis reduced HFD-induced hepatic lipid accumulation. Furthermore, short-term PCPA treatment prevented HCD-induced hepatic steatosis without affecting glucose tolerance and browning of subcutaneous adipose tissue. Gene expression analysis revealed that the expressions of genes involved in de novo lipogenesis and triacylglycerol synthesis were downregulated by short-term PCPA treatment as well as long-term PCPA treatment.

Conclusion

Short-term inhibition of serotonin synthesis prevented hepatic lipid accumulation without affecting systemic insulin sensitivity and energy expenditure, suggesting the direct steatogenic effect of serotonin in liver.

   
Keywords:
Diabetes mellitusFatty liverLipogenesisObesitySerotonin
 

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