• Journal of Life Science
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• v.31 no.5
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• pp.464-474
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• 2021

Inflammation induced by metabolic syndromes, cancers, injuries, and sepsis can alter cellular metabolism by reducing mitochondrial function via oxidative stress, thereby resulting in neuropathy and muscle atrophy. In this study, we investigated whether butyrate, a short chain fatty acid produced by gut microbiota, could prevent mitochondrial dysfunction and muscle atrophy induced by lipopolysaccharide (LPS) in the C2C12 cell line. LPS-activated MAPK signaling pathways increased the levels of the mitochondrial fission signal, p-DRP1 (Ser616), and the muscle atrophy marker, atrogin 1. Interestingly, butyrate significantly inhibited the phosphorylation of JNK and p38 and reduced the atrogin 1 level in LPS-treated C2C12 cells while increasing the phosphorylation of DRP1 (Ser637) and levels of mitofusin2, which are both mitochondrial fusion markers. Next, we investigated the effect of MAPK inhibitors, finding that butyrate had the same effect as JNK inhibition in C2C12 cells. Also, butyrate inhibited the LPS-induced expression of pyruvate dehydrogenase kinase 4 (PDK4), resulting in decreased PDHE1α phosphorylation and lactate production, suggesting that butyrate shifted glucose metabolism from aerobic glycolysis to oxidative phosphorylation. Finally, we found that these effects of butyrate on LPS-induced mitochondrial dysfunction were caused by its antioxidant effects. Thus, our findings demonstrate that butyrate prevents LPS-induced muscle atrophy by improving mitochondrial dynamics and metabolic stress via the inhibition of JNK phosphorylation. Consequently, butyrate could be used to improve LPS-induced mitochondrial dysfunction and myopathy in sepsis.

• Journal of Arbitration Studies
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• v.17 no.1
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• pp.183-215
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• 2007

The purpose of this paper is to study of WTO regulations related FTA such as Understanding on the Interpretation of Article XXIV of the General Agreement on Tariffs and Trade(GATT) 1994 and General Agreement on Trade in Service(GATS). In this study, the First introduced FTA rules of WTO in the chapter 2. The WTO agreement includes the "General Agreement on Tariffs an Trade(GATT) 1994". This instrument, known as "GATT 1994", is based on upon the original General Agreement on Tariffs and Trade referred to as "GATT 1947". The Second analyzed the relations between FTA and Article XXIV of GATT 1994 in the chapter 3. The Article XXIV of GATT 1994 is an agreement between the distinctive members for liberalizing trade. The Article XXIV of GATT 1994 is consist of three parts such as customs unions, free-trade area, and interim agreements that WTO is referred to as "Regional Trade Agreement(RTA)". There is a difference between the customs unions and the free-trade area. In the customs unions rules, the members should have the same tarifficatio and the same trade provision against non-members, but in the free-trade are a rules, the member is not necessary to have the same tarifficatio and the same trade provision against non-members. But, the both rules have a liberalization of trade in a common as a revoking tariffs and the government regulations for interfering with trade. In this case, however, the both rules include an inconsistency ele ment under WTO rules such as Most-Favoured-Nation Treatment(MFN) and National Treatment on Internal Taxation and Regulation(NTITR). This study reviewed neither inconsistency nor consistency on the both rules with the RTA of WTO under Article XXIV of GATT 1994. The Third analyzed the relations between FTA and Article V of GATS under WTO in the chapter 4. The GATS is a rule of WTO for the growing importance of trade in services for the growth and development of the world conomy. The GATS is a new rule rather than GATT's rule for concerning goods trade. The Article V of GATS under WTO is a rule that makes based on upon the Article XXIV of GATT. Therefore, If it is to be examined the Article V of GATS, it should be referred to a and an interpretation of the text of the Article XXIV of GATT. However, the Article V of GATS is on the undeveloped stage compare to the Article XXIV of GATT. Because, the statistics of WTO showed that the RTAs under the Article XXIV of GATT have 150 cases completed between nations, but the RTAs under the Article IV of GATS have 10 cases completed between nations. The Forth examined the interpretation of FTA rules under WTO in the chapter 5. Concerning the consistency issue of customs unions and free-trade area under the Article XXIV of GATT, the working parties in customs unions and in free-trade area have been reviewed the consistency is sue which had been not if to GATT. However, the parties finished to get up with one accord the both that are a consistency of argument and an inconsistency of argument with the interpretation of the Article XXIV of GATT. The interpretation of the Article XXIV of GATT has been raised as the issues when EEC by Rome Treaty established in 1957. However, the consistency is sue only agreed 6 working parties out of 69 working parties finished the reviewing of the interpretation up to the end of 1994. Also the consistency issue concerned with the special privilege measure of the customs unions and tree-trade area under the Article XXIV of GATT discussed only 3 cases between working parties up to now and did not accepted as an issue for working parties' report. In conclusion in the chapter 6, this study raised the issues of WTO that are a conference of a new round under WTO and the issues of clarity between FTA rule and WTO regulation.