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Department of Biomedical Sciences

 

 

 
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蕭明熙(Ming-Shi Shiao)

Ming-Shi Shiao

Position

Visiting Professor

Education

Ph.D. in Bioorganic Chemistry, Brown

E-mail

msshiao@mail.cgu.edu.tw

Office Tel

+886-3-211-8800 ext.3495

Fax

+886-3-211-8700

Laboratory

Laboratory of Chemical Biology

Specialty

Chemical biology、lipid metabolism、metabolomics

Lab & Research Interest

1. Diabetes-induced metabolic disorders and the effects of resveratrol for improving lipid, energy, and BCAA metabolism and reducing of inflammation and muscle wasting. Chen KH, Cheng ML, Jing YH, Chiu DT, Shiao MS*, Chen JK*. Resveratrol ameliorates metabolic disorders and muscle wasting in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab 301: E853–E863, 2011. First published July 26, 2011; doi:10.1152/ajpendo.00048.2011.

Diabetes mellitus (DM) is characterized by dysregulated energy metabolism. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in diabetic animals. However, its overall in vivo effects on energy metabolism and the underlying mechanism require further investigation. In the present study, electrospray ionization-tandem mass spectrometry was employed to characterize the urine and plasma metabolomes of control, streptozotocin-induced DM and RSV-treated DM rats. Using principal component analysis (PCA) and heat map analysis, we discovered significant differences among control and experimental groups. RSV treatment significantly reduced the metabolic abnormalities in DM rats. Compared with the age-matched control rats, the level of carnitine was lower, and the levels of acetylcarnitine and butyrylcarnitine were higher in the urine and plasma of DM rats. RSV treatment ameliorated the deranged carnitine metabolism in DM rats. In addition, RSV treatment attenuated the diabetic ketoacidosis and muscle protein degradation, as evidenced from the attenuation of elevated urinary methyl-histidine and plasma branched-chain amino acids levels in DM rats. The beneficial effects of RSV in DM rats were correlated with activation of hepatic AMP-activated protein kinase and SIRT1 expression, increase of hepatic and muscular mitochondrial biogenesis and inhibition of muscle NF-kB activities. We concluded that RSV possesses multiple beneficial metabolic effects in insulin-deficient DM rats, particularly in improving energy metabolism and reducing protein wasting.

2. Metabolomics as a tool for biomarker discovery in metabolic syndrome, diabetes, and diabetes-accelerated atherosclerosis. Huang CF, Cheng ML, Fan CM, Hong CY, Shiao MS*. Nicotinuric acid: A potential marker of metabolic syndrome through a metabolomics-based approach. Diabetes Care (2013, in press)

Metabolic syndrome is a multifaceted disorder and considered a universal epidemic puts patients on the road to type 2 diabetes and atherosclerotic cardiovascular diseases. Although urine metabolomics has potential utility in metabolic profiling because urine metabolites analysis reflects global outflux of metabolic change, a surrogate biomarker in urine in fully reflecting features of metabolic syndrome has not been explored. Therefore, the aim of this study was to elicit a potential biomarker to picture metabolic syndrome by collecting data on subjects with overweight, dyslipidemia, hypertension or impaired glucose tolerance and taking a metabolomics approach to analyze the metabolites of urine revealed in metabolic syndrome.

3. Collaborative studies on the role of microRNA-122 in hepatic lipid homeostasis, fatty liver and carcinogenesis. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. Tsai WC. Hsu SD, Hsu CS,1 Lai TC, Chen SJ, Shen R, Huang Y, Chen HC, Lee CH, Tsai TF, Hsu MT, Wu JC, Huang HD, Shiao MS, Hsiao M, Tsou AP. J Clin Invest. 2012;122:2884-2897. (NMR spectroscopy was used as a key tool in the metabolomics part of this collaborative study. Prof. AP Tsou, YMU is the principal investigator.)

MicroRNA-122 (miR-122), which accounts for 70% of the liver’s total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined. We demonstrated that mice lacking the gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These mice exhibited a striking disparity in HCC incidence based on sex, with a male-to-female ratio of 3.9:1, which recapitulates the disease incidence in humans. Impaired expression of microsomal triglyceride transfer protein (MTTP) contributed to steatosis, which was reversed by in vivo restoration of Mttp expression. We found that hepatic fibrosis onset can be partially attributed to the action of a miR-122a target, the Klf6 transcript. In addition, Mir122a–/– livers exhibited disruptions in a range of pathways, many of which closely resemble the disruptions found in human HCC. Importantly, the reexpression of miR-122a reduced disease manifestation and tumor incidence in Mir122a–/– mice. This study demonstrates that mice with a targeted deletion of the Mir122a gene possess several key phenotypes of human liver diseases, which provides a rationale for the development of a unique therapy for the treatment of chronic liver disease and HCC.

Publications

Publications:

  1. Shiao MS, Chiu JJ, Chang BW, Wang J, Jen WP, Wu YJ, Chen YL. 2008. In search of antioxidants and anti-atherosclerotic agents from herbal medicines. Biofactors., 34, 147-57.
     
  2. Juo CG, Chiu DT, Shiao MS*. 2008. Liquid chromatography-mass spectrometry in metabolite profiling. Biofactors., 34, 159-69.
     
  3. Hou CJ, Tsai CH, Su CH, Wu YJ, Chen SJ, Chiu JJ, Shiao MS, Yeh HI. 2008. Diabetes reduces aortic endothelial gap junctions in ApoE-deficient mice: simvastatin exacerbates the reduction. J Histochem Cytochem., 56, 745-52.
     
  4. Chen TY, Lin BC, Shiao MS, Pan BS. 2008. Lipid-lowering and LDL-oxidation inhibitory effects of aqueous extract of freshwater clam (Corbicula fluminea)--using tilapia as an animal model. J Food Sci., 73, H148-54.
     
  5. Chen HI, Kao SL, Tsai MH, Shiao MS, Jen CJ. 2009. Exercise training modulates the effects of lipoproteins on acetylcholine-induced endothelial calcium signaling in rat aortas. Exp Biol Med (Maywood)., 234, 323-31.
     
  6. Yang TL, Lin FY, Chen YH, Chiu JJ, Shiao MS, Tsai CS, Lin SJ, Chen YL. 2011. Salvianolic acid B inhibits low-density lipoprotein oxidation and neointimal hyperplasia in endothelium-denuded hypercholesterolaemic rabbits. J Sci Food Agric., 91(1), 134-41.
     
  7. Chen YR, Huang HB, Lo CJ, Wang CC, Su CL, Liu HT, Shiao MS, Lin TH, Chen YC. 2011. Aβ(40) (L17A/F19A) mutant diminishes the aggregation and neurotoxicity of Aβ(40). Biochem Biophys Res Commun., 405(1), 91-5.
     
  8. Leu YL, Wang PH, Shiao MS, Ismail W, Chiang YR*. 2011. A novel testosterone catabolic pathway in bacteria. J Bacteriol., 193(17), 4447-55.
     
  9. Tang CH, Tsao PN, Chen CY, Shiao MS, Wang WH, Lin CY*. 2011. Glycerophosphocholine molecular species profiling in the biological tissue using UPLC/MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci., 879(22), 2095-106.
     
  10. Cheng ML, Shiao MS, Chiu DT, Weng SF, Tang HY, Ho HY*. 2011. Biochemical disorders associated with antiproliferative effect of dehydroepiandrosterone in hepatoma cells as revealed by LC-based metabolomics. Biochem Pharmacol., 82(11), 1549-61.
     
  11. Chen KH, Cheng ML, Jing YH, Chiu DT, Shiao MS*, Chen JK*. 2011. Resveratrol ameliorates metabolic disorders and muscle wasting in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab., 301(5), E853-63.
     
  12. Wang CC, Huang HB, Tsay HJ, Shiao MS, Wu WJ, Cheng YC*, Lin TH*. 2012. Characterization of Aβ aggregation mechanism probed by congo red. J Biomol Struct Dyn., 30(2), 160-9.
     
  13. Tsai WC, Hsu SD, Hsu CS, Lai TC, Chen SJ, Shen R, Huang Y, Chen HC, Lee CH, Tsai TF, Hsu MT, Wu JC, Huang HD, Shiao MS, Hsiao M, Tsou AP*. 2012. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest., 122(8), 2884-97.
     
  14. Ho HY, Cheng ML, Shiao MS, Tsun-Yee Chiu D*. 2013. Characterization of Global Metabolic Responses of G6PD-Deficient Hepatoma Cells to Diamide-Induced Oxidative Stress. Free Radic Biol Med., 54, 71-84.
     
  15. Huang CF, Mei-Ling Cheng ML, Fan CM, Hong CY, Shiao MS*. (in press). Nicotinuric acid: A potential marker of metabolic syndrome through a metabolomics-based approach. Diabetes Care, doi: 10.2337/dc12-1067, 1-3.