Effects of Amomum cadamomum Linne Extract on TNF-α-induced Inflammation and Insulin Resistance in 3T3-L1 Adipocytes
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Amomum cadamomum Linne (ACL) has long been utilized against the inhibited qi movement related diseases such as dyspepsia, acute gastroenteritis, vomiting and diarrhea in Korean medicine. We speculated that ACL could improve the metabolic disorders such as obesity and type 2 diabetes through removing the phlegm-dampness and promoting the qi movement or stagnation. This study was designed to investigate effects and molecular mechanisms of ACL extract on the improvement of adipocyte dysfunction induced by TNF-α in 3T3-L1 adipocytes. Potential roles of ACL extract in the lipogenesis, inhibition of inflammatory cytokines and insulin resistance, were investigated in this study. Also, we examined the adipose genes and signaling molecules related to insulin resistance and glucose uptake to elucidate its mechanism. Our data demonstrated that TNF-α significantly incresed the release of lipid droplets and the production of MCP-1 and IL-6 from adipocytes. In gene expression, TNF-α reduced the expression of aP2, PPARγ, C/EBPα, GLUT4, and IRS-1 related to lipogenesis and insulin sesitivity, while TNF-α increased the expression of MCP-1 related to inflammation. In addition, TNF-α down-regulated the PPARγ and IRS-1 protein and up-regulated the IRS-1 Ser307 phosphorylation. These alterations induced by TNF-α were prevented by the treatment of ACL extract. Thus, our results indicate that ACL extract can be used to prevent from the TNF-α-induced adipocyte dysfunction through insulin and PPARγ pathways.
Abstract
Amomum cadamomum Linne (ACL) has long been utilized against the inhibited qi movement related diseases such as dyspepsia, acute gastroenteritis, vomiting and diarrhea in Korean medicine. We speculated that ACL could improve the metabolic disorders such as obesity and type 2 diabetes through removing the phlegm-dampness and promoting the qi movement or stagnation. This study was designed to investigate effects and molecular mechanisms of ACL extract on the improvement of adipocyte dysfunction induced by TNF-α in 3T3-L1 adipocytes. Potential roles of ACL extract in the lipogenesis, inhibition of inflammatory cytokines and insulin resistance, were investigated in this study. Also, we examined the adipose genes and signaling molecules related to insulin resistance and glucose uptake to elucidate its mechanism. Our data demonstrated that TNF-α significantly incresed the release of lipid droplets and the production of MCP-1 and IL-6 from adipocytes. In gene expression, TNF-α reduced the expression of aP2, PPARγ, C/EBPα, GLUT4, and IRS-1 related to lipogenesis and insulin sesitivity, while TNF-α increased the expression of MCP-1 related to inflammation. In addition, TNF-α down-regulated the PPARγ and IRS-1 protein and up-regulated the IRS-1 Ser307 phosphorylation. These alterations induced by TNF-α were prevented by the treatment of ACL extract. Thus, our results indicate that ACL extract can be used to prevent from the TNF-α-induced adipocyte dysfunction through insulin and PPARγ pathways.
참고문헌 (27)
- Kahn, B. B., "Obesity and insulin resistance", J. Clin. Invest, 106, pp.473~481 (2000)
- Kim, J. A., "Role of mitochondrial dysfunction in insulin resistance", Circ. Res, 102, pp.401~414 (2008)
- Chen, X. H., "TNF-alpha induces mitochondrial dysfunction in 3T3-L1 adipocytes. Mol", Cell. Endocrinol., 328, pp.63~69 (2010)
- Anusree, S. S., "Insulin resistance by TNF-alpha is associated with mitochondrial dysfunction in 3T3-L1 adipocytes and is ameliorated by punicic acid, a PPARgamma agonist", Mol. Cell. Endocrinol., 413, pp.120~128 (2015)
- Cawthorn, W. P., "TNF-alpha and adipocyte biology", FEBS Lett, 582, pp.117~131 (2008)
- Daniele, G., "The inflammatory status score including IL-6, TNF-alpha, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus", Acta Diabetol, 51, pp.123~131 (2014)
- Yeo, J., "Effects of a multi-herbal extract on type 2 diabetes", Chin Med, 6, pp.10~ (2011)
- Suneetha, W. J., "Cardamom extract as inhibitor of human platelet aggregation", Phytother Res, 19, pp.437~440 (2005)
- Roberts, L. D., "Metabolic phenotyping of a model of adipocyte differentiation", Physiol. Genomics., 39, pp.109~119 (2009)
- Im, S. S., "Regulation of GLUT4 gene expression by SREBP-1c in adipocytes", Biochem. J., 399, pp.131~139 (2006)
- Jitrapakdee, S., "The peroxisome proliferator-activated receptor-gamma regulates murine pyruvate carboxylase gene expression in vivo and in vitro", J. Biol. Chem., 280, pp.27466~27476 (2005)
- Wheatcroft, S. B., "IGF-binding protein-2 protects against the development of obesity and insulin resistance", Diabetes, 56, pp.285~294 (2007)
- Ahn, J., "Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt", beta-catenin signaling, 2010, pp.298, C1510~C1516
- Brannmark, C., "Insulin signaling in type 2 diabetes: experimental and modeling analyses reveal mechanisms of insulin resistance in human adipocytes", J. Biol. Chem., 288, pp.9867~9880 (2013)
- Chen, L., "Mechanisms Linking Inflammation to Insulin Resistance", Int J Endocrinol, 2015, pp.508409~ (2015)
- Lee, O. H., "Effect of ginsenosides Rg3 and Re on glucose transport in mature 3T3-L1 adipocytes", Phytother Res, 25, pp.768~773 (2011)
- Qatanani, M., "Mechanisms of obesity- associated insulin resistance: many choices on the menu", Genes Dev, 21, pp.1443~1455 (2007)
- Anusree, S. S., "Insulin resistance by TNF-alpha is associated with mitochondrial dysfunction in 3T3-L1 adipocytes and is ameliorated by punicic acid, a PPARgamma agonist", Mol. Cell. Endocrinol., 413, pp.120~128 (2015)
- Hotamisligil, G. S., "Inflammation and metabolic disorders", Nature, 444, pp.860~867 (2006)
- Maury, E., "Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome", Mol. Cell. Endocrinol., 314, pp.1~16 (2010)
- Kahn, S. E., "Mechanisms linking obesity to insulin resistance and type 2 diabetes", Nature, 444, pp.840~846 (2006)
- Serrano-Marco, L., "The peroxisome proliferator- activated receptor (PPAR) beta", delta agonist GW501516 inhibits IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation and insulin resistance in human liver cells, 2012, pp.55, 743~751
- Kanda, H., "MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity", J. Clin. Invest., 116, pp.1494~1505 (2006)
- Xu, H., "Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance", J. Clin. Invest., 112, pp.1821~1830 (2003)
- Aguirre, V., "Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action", J. Biol. Chem., 277, pp.1531~1537 (2002)
- Gao, Z., "Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex", The J. Biol. Chem., 277, pp.48115~48121 (2002)
- Zhande, R., "Molecular mechanism of insulin-induced degradation of insulin receptor substrate 1", Mol. Cell. Endocrinol., 22, pp.1016~1026 (2002)