S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Theses (Master's Degree_분자의학 및 바이오제약학과)
Role of Fibroblast Growth Factor 13 in fatty acid induced insulin resistance in skeletal muscle : FGF13 이 지방산에 의한 골격근 인슐린 저항성에 미치는 영향
- 융합과학기술대학원 분자의학 및 바이오제약학과
- Issue Date
- 서울대학교 융합과학기술대학원
- Fibroblast Growth Factor 13 ; Fibroblast Growth Factor Homologous Factor 2 ; insulin resistance ; saturated fatty acid ; palmitate ; type 2 diabetes ; obesity ; MAPK
- 학위논문 (석사)-- 서울대학교 융합과학기술대학원 : 분자의학 및 바이오제약학과, 2015. 8. 박경수.
- Fibroblast growth factors (FGFs) are categorized as paracrine, endocrine and intracrine and are involved in development, cell proliferation, differentiation and metabolism. The secreted FGFs function by interacting with FGF receptors while intracellular non-secreting FGFs interact with voltage gated sodium channels. FGF13 is a member of the intracellular fibroblast growth factor family. FGF13 has various transcript variants by alternatively splicing at 5 end. This study was aimed to investigate the regulation of FGF13 in diet induced obese mice and in fatty acid induced insulin resistance in skeletal muscle. FGF13 isoform 1 was mainly distributed in brain and adipose tissues while FGF13 isoform 2 was predominantly expressed in heart and muscle. I have demonstrated that both muscle and adipose expression of FGF13 was reduced in 12 week high fat fed mice. 24 hour exposure to palmitate decreased FGF13 isoform 2 in C2C12 muscle cells. I also found that palmitate decreased FGF13 through TLR4 pathway. Moreover, when FGF13 was knockdown, immediate early genes of downstream ERK/JNK was suppressed. To further investigate the role of FGF13 in insulin signaling model, FGF13 was overexpressed or knocked down on C2C12 myotubes. I was able to confirm that overexpressing FGF13 could recover AKT signaling during palmitate treatment while knockdown reduced phospho-AKT. Moreover, overexpression of FGF13 reduced phospho-JNK which is known to affect insulin signaling. These findings suggests that FGF13 protein have a role in insulin signaling pathway in fatty acid induced insulin resistance.