GIST Repository
College of Life Sciences and Medical Engineering
Department of Biomedical Science and Engineering
4. Theses(Ph.D)
The effects of serotonin by Tph1 and Htr2b on skeletal muscle
- Abstract
- -fat diet, and the role of serotonin in skeletal muscle. The findings suggest that central serotonin in the human brain regulates fatty acid metabolism, mitochondrial biogenesis, and quality control. TPH1 expressions in the small intestine and colon have significant associations with hormone and nutrition regulation. Additionally, inhibiting Tph1 and Htr2b increases AMPK activity, glucose uptake, and myofiber size and decreases lipid droplet accumulation in HFD mice’s skeletal muscle. These results indicate improved insulin resistance and myosteatosis in skeletal muscle by lack of serotonin by Tph1 and Htr2b on skeletal muscle. These results provide strong evidence that serotonin plays significant roles in critical pathways such as mitochondrial homeostasis, energy metabolism, and organ development.
- Issued Date
- 2025
- Type
- Thesis
- Alternative Author(s)
- SuhyeonPark
- Department
- 대학원 의생명공학과
- Advisor
- Oh, Chang-Myung
- Table Of Contents
- Abstract ․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ ⅰ
Contents ․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ ⅲ
List of tables .․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ ⅶ
List of figures ․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ ⅷ
CHAPTER 1.
I. INTRODUCTION 9․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
1. 1. Obesity ․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ 9
1. 2. Serotonin ․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ 10
1. 2. 1. Peripheral serotonin ․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ 10
1. 2. 2. The role of serotonin in metabolic disorders 12․․․․․
II. RESULTS 13․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
2. 1. TPH expression in human tissue 13․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
2. 2. Transcriptome analysis in brain according to TPH2 expression
15․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
2. 3. Transcriptome analysis in intestine and adipose tissue
according to TPH1 expression 17․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
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2. 4. Transcriptome analysis in white adipose tissue according to
TPH1 expression .․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ 19
2. 5. The role of serotonin in mitochondria 22․․․․․․․․․․․․․․․․․․․․․․․․․․․․
2. 6. Metabolite changes according to TPH expression 23․․․․․․․․․․
Ⅲ. DISCUSSION 27․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
Ⅳ. METERIALS AND METHODS 29․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ ․․․․․․․
4. 1. Data collection 29․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
4. 2. Data analysis 29․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
. CONCLUSIONSⅤ 30․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
. SUPPLEMENTARY DATAⅥ 31․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
. REFERENCESⅦ 45․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
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CHAPTER 2.
I. INTRODUCTION 57․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
1. 1. Obesity 57․․․․․․․․․․․․․․․․․․․․․․․․
1. 2. Skeletal muscle ․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․. 57
1. 3. Seorotnin and skeletal muscle ․․․․․․․ 58
II. RESULTS 59․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
2. 1. Inhibition of 5-HT synthesis improves glucose uptake
signaling in C2C12 myotubes 59․․․․․․․․․․․․․․․․․․․․․․․
2. 2. Inhibition of 5-HT synthesis in skeletal muscle protects against
HFD-induced insulin resistance 62․․․․․․․․․․․․․․․․․․․․․․․․
2. 3. Inhibition of 5-HT synthesis in skeletal muscle protects against
HFD-induced myosteatosis 65․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
2. 4. 5-HT regulates glucose metabolism through HTR2b in C2C 12
myotubes 69․․․․․․․․․․․․․․․․․․․․․․․․
2. 5. Inhibition of HTR2b signaling in skeletal muscle protects
against HFD-induced myosteatosis 72․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․ ․․
2. 6. Inhibition of HTR2b signaling in skeletal muscle leads to
transcriptional changes in energy metabolism 75
Ⅲ. DISCUSSION 78․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
Ⅳ. METERIALS AND METHODS 81․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
4. 1. Reagents 81․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
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4. 2. Cell cultures and treatments 81․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
4. 3. Animals and diets 82․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
4. 4. Glucose and insulin tolerance tests 83․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
4. 5. Protein extraction and western blot analysis 83
4. 6. RNA sequencing and analysis 84․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
4. 7. Serotonin measurement 84․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
4. 8. Hyperinsulinemic-euglycemic clamp test 85․․․․․․․․․․
4. 9. ECAR assay 85․․․․․․․․․․․․․․․․․․․․․․․․․․
4. 10. Histological analysis 86․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
. CONCLUSIONSⅤ 88․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
. SUPPLEMENTARY DATAⅥ 89․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
. REFERENCESⅦ 97․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․․
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