2012 Fiscal Year Final Research Report
Role of L-Tryptophan on NAFLD and NASH
| Project/Area Number |
23790787
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Gifu University |
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Principal Investigator |
OSAWA Yosuke 岐阜大学, 医学系研究科, 助教 (60447787)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 脂肪肝 / 脂肪肝炎 / トリプトファン / セロトニン / オートファジー |
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| Research Abstract |
Nonalcoholic fatty liver disease is one of the most common liver diseases. L-Tryptophan and its metabolite serotonin are involved in hepatic lipid metabolism and inflammation. However, it is unclear whether L-tryptophan promotes hepatic steatosis. To explore this issue, we examined the role of L-tryptophan in mouse hepatic steatosis by using a high -fat and high-fructose diet (HFHFD) model. L-Tryptophan treatment in combination with a HFHFD exacerbated hepatic steatosis, expression of HNE-modified proteins, hydroxyproline content, and serum ALT levels, whereas L-tryptophan alone did not result in these effects. We also found that L-Tryptophan treatment increasesserum serotonin levels. The introduction of adenoviral aromatic amino acid decarboxylase (AADC), which stimulates the serotonin synthesis from L-tryptophan, aggravated hepatic steatosis induced by the HFHFD. The fatty acid-induced accumulation of lipid was further increased by serotonin treatmen t in cultured hepatocytes. These results suggest that L-tryptophan increases the sensitivity to hepatic steatosis through serotonin production. Furthermore, L-tryptophan treatment, adenoviral AADC introduction, and serotonin treatment induced phosphorylation of the mammalian target of rapamycin (mTOR) and a potent mTOR inhibitor rapamycin attenuated hepatocyte lipid accumulation induced by fatty acid with serotonin. These results suggest the importance of mTOR activation for the exacerbation of hepatic steatosis. In conclusion, L-tryptophan exacerbates hepatic steatosis induced by HFHFD through serotonin-mediated activation of mTOR.
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[Journal Article] Involvement of KRAS G12A mutation in the IL-2-independent growth of a human T-LGL leukemia cell line, PLT-2.2012
Author(s)
Mizutani N, Ito H, Hagiwara K, Kobayashi M, Hoshikawa A, Nishida Y , Takagi A, Kojima T, Suzuki M, Osawa Y, Ohnishi K, Daibata M, Murate T.
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Journal Title
Nagoya J Med Sci
Volume: 74
Pages: 261-271
Peer Reviewed
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[Journal Article] L-Tryptophan-kynurenine pathway metabolites regulate type I IFNs of acute viral myocarditis in mice.2012
Author(s)
Hoshi M, Matsumoto K, Ito H, Ohtaki H, Arioka Y, Osawa Y, Yamamoto Y, Matsunami H, Hara A, Seishima M, Saito K.
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Journal Title
J Immunol
Volume: 188
Pages: 3980-3987
Peer Reviewed
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[Journal Article] L-Tryptophan-mediated enhancement of susceptibility to nonalcoholic fatty liver disease is dependent on the mammalian target of rapamycin.2011
Author(s)
Osawa Y, Kanamori H, Seki E, Hoshi M,Ohtaki H, Yasuda Y, Ito H, Suetsugu A,Nagaki M, Moriwaki H, Saito K, Seishima M.
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Journal Title
J Biol Chem
Volume: 286
Pages: 34800-34808
Peer Reviewed
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[Journal Article] Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression.2011
Author(s)
Osawa Y, Seki E, Kodama Y, Suetsugu A, Miura K, Adachi M, Ito H, Shirator,i Y, Banno Y, Olefsky JM, Nagaki M, Moriwaki H, Brenner DA, Seishima M.
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Journal Title
FASEB J
Volume: 25
Pages: 1133-1144
Peer Reviewed
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