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Original Article
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
  • 5,562 View
  • 95 Download
  • 25 Web of Science
  • 23 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  
  • Peripheral Serotonin Controls Dietary Fat Absorption and Chylomicron Secretion via 5-HT4 Receptor in Males
    Fitore Raka, Simon Hoffman, Asal Nady, Henry Guan, Rianna Zhang, Huaqing Wang, Waliul I Khan, Khosrow Adeli
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  • Design, Synthesis, and Biological Evaluation of New Peripheral 5HT2A Antagonists for Nonalcoholic Fatty Liver Disease
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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
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Review
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
  • 8,329 View
  • 184 Download
  • 75 Web of Science
  • 79 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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