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Sangkyu Park  (Park S) 2 Articles
Obesity and Metabolic Syndrome
Inhibition of Serotonin Synthesis Induces Negative Hepatic Lipid Balance
Jun Namkung, Ko Eun Shong, Hyeongseok Kim, Chang-Myung Oh, Sangkyu Park, Hail Kim
Diabetes Metab J. 2018;42(3):233-243.   Published online April 25, 2018
DOI: https://doi.org/10.4093/dmj.2017.0084
  • 4,822 View
  • 87 Download
  • 24 Web of Science
  • 22 Crossref
AbstractAbstract PDFPubReader   
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.

Citations

Citations to this article as recorded by  
  • A new serotonin 2A receptor antagonist with potential benefits in Non-Alcoholic Fatty Liver Disease
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  • Serotonin reuptake transporter deficiency promotes liver steatosis and impairs intestinal barrier function in obese mice fed a Western‐style diet
    Louisa Filipe Rosa, Eva Haasis, Annkathrin Knauss, Daria Guseva, Stephan C. Bischoff
    Neurogastroenterology & Motility.2023;[Epub]     CrossRef
  • Probiotics counteract hepatic steatosis caused by ketogenic diet and upregulate AMPK signaling in a model of infantile epilepsy
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  • Research Progresses for 5-Hydroxytryptamine in Lipid Metabolism
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    Bioprocess.2022; 12(01): 1.     CrossRef
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    Hang Yin, Anhua Shi, Junzi Wu
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  • Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A
    Takashi Owaki, Kenya Kamimura, Masayoshi Ko, Itsuo Nagayama, Takuro Nagoya, Osamu Shibata, Chiyumi Oda, Shinichi Morita, Atsushi Kimura, Takeki Sato, Toru Setsu, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Shuji Terai
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  • Pancreatic Sirtuin 3 Deficiency Promotes Hepatic Steatosis by Enhancing 5-Hydroxytryptamine Synthesis in Mice With Diet-Induced Obesity
    Xing Ming, Arthur C.K. Chung, Dandan Mao, Huanyi Cao, Baoqi Fan, Willy K.K. Wong, Chin Chung Ho, Heung Man Lee, Kristina Schoonjans, Johan Auwerx, Guy A. Rutter, Juliana C.N. Chan, Xiao Yu Tian, Alice P.S. Kong
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  • Peripheral Selective Oxadiazolylphenyl Alanine Derivatives as Tryptophan Hydroxylase 1 Inhibitors for Obesity and Fatty Liver Disease
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  • Metabolic Disturbances in Rat Sublines with Constitutionally Altered Serotonin Homeostasis
    Maja Kesić, Petra Baković, Ranko Stojković, Jasminka Štefulj, Lipa Čičin-Šain
    International Journal of Molecular Sciences.2021; 22(10): 5400.     CrossRef
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    Journal of Clinical Investigation.2021;[Epub]     CrossRef
  • Green tea and selenium-enriched green tea ameliorates non-alcoholic fatty liver disease through peripheral 5-hydroxytryptamine signals in high-fat diet-fed mice
    Lin Zhang, Jia-Ying Xu, Ya-Fang Du, Zhang-Min Wang, Jian-Xiang Li, N. Ou-Yang, Yan Wang, Xue-Bin Yin, Li-Qiang Qin
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    Michael Bader
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  • One-Carbon Metabolism in Fatty Liver Disease and Fibrosis: One-Carbon to Rule Them All
    da Silva Robin P, Eudy Brandon J, Deminice Rafael
    The Journal of Nutrition.2020; 150(5): 994.     CrossRef
  • Design, Synthesis, and Biological Evaluation of New Peripheral 5HT2A Antagonists for Nonalcoholic Fatty Liver Disease
    Minhee Kim, Inseon Hwang, Haushabhau S. Pagire, Suvarna H. Pagire, Wonsuk Choi, Won Gun Choi, Jihyeon Yoon, Won Mi Lee, Jin Sook Song, Eun Kyung Yoo, Seung Mi Lee, Mi-jin Kim, Myung Ae Bae, Dooseop Kim, Heejong Lee, Eun-Young Lee, Jae-Han Jeon, In-Kyu Lee
    Journal of Medicinal Chemistry.2020; 63(8): 4171.     CrossRef
  • Hepatic fibrosis is associated with total proteinuria in Korean patients with type 2 diabetes
    Eugene Han, Yongin Cho, Kyung-won Kim, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-wan Lee
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  • Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule
    Julian M Yabut, Justin D Crane, Alexander E Green, Damien J Keating, Waliul I Khan, Gregory R Steinberg
    Endocrine Reviews.2019; 40(4): 1092.     CrossRef
  • 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 Par
    Nature Communications.2018;[Epub]     CrossRef
Obesity and Metabolic Syndrome
Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity
Chang-Myung Oh, Sangkyu Park, Hail Kim
Diabetes Metab J. 2016;40(2):89-98.   Published online March 27, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.2.89
  • 7,139 View
  • 162 Download
  • 68 Web of Science
  • 73 Crossref
AbstractAbstract PDFPubReader   

Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine that has various functions in both neuronal and non-neuronal systems. In the central nervous system, 5-HT regulates mood and feeding behaviors as a neurotransmitter. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. Unfortunately, some drugs were withdrawn due to the development of unwanted peripheral side effects, such as valvular heart disease and pulmonary hypertension. Recent studies revealed that peripheral 5-HT plays an important role in metabolic regulation in peripheral tissues, where it suppresses adaptive thermogenesis in brown adipose tissue. Inhibition of 5-HT synthesis reduced the weight gain and improved the metabolic dysfunction in a diet-induced obesity mouse model. Genome-wide association studies also revealed genetic associations between the serotonergic system and obesity. Several genetic polymorphisms in tryptophan hydroxylase and 5-HT receptors were shown to have strong associations with obesity. These results support the clinical significance of the peripheral serotonergic system as a therapeutic target for obesity and diabetes.

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Diabetes Metab J : Diabetes & Metabolism Journal