TY - JOUR
T1 - Hepatic overexpression of dominant negative Mlx improves metabolic profile in diabetes-prone C57BL/6J mice
AU - Iizuka, Katsumi
AU - Takeda, Jun
AU - Horikawa, Yukio
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (K. Iizuka), the ONO Medical Research Foundation (K. Iizuka), the Kao Research Council for the Study of Healthcare Science (K. Iizuka), and in part by a New Energy and Industrial Technology Development Organization grant (Y. Horikawa). We apologize to authors whose work was not been cited because of limited space.
PY - 2009/2/6
Y1 - 2009/2/6
N2 - Mlx and ChREBP form a heterodimer to regulate glucose-mediated gene expression in the liver. This study was performed to determine if the metabolic syndrome might be improved using dominant negative Mlx (dnMlx). An adenovirus bearing dnMlx was constructed and used to test the inhibitory effect of dnMlx on lipogenesis both in vitro and in vivo. Adenoviral overexpression of dnMlx in rat hepatocytes inhibited expression of glucose-regulated genes, including Chrebp and Transketolase, which constitute a positive feedback loop in the regulation of Chrebp gene expression. Adenoviral overexpression of dnMlx in 25-week-old male C57BL/6J mice reduced hepatic triglyceride contents and improved glucose intolerance by inhibiting expression of Glucose-6-phosphatase and Elovl6 mRNA in addition to lipogenic enzymes. In conclusion, overexpression of dnMlx improves glucose intolerance by inhibiting expression not only of lipogenic enzymes but also other important genes such as Glucose-6-phosphatase and Elovl6.
AB - Mlx and ChREBP form a heterodimer to regulate glucose-mediated gene expression in the liver. This study was performed to determine if the metabolic syndrome might be improved using dominant negative Mlx (dnMlx). An adenovirus bearing dnMlx was constructed and used to test the inhibitory effect of dnMlx on lipogenesis both in vitro and in vivo. Adenoviral overexpression of dnMlx in rat hepatocytes inhibited expression of glucose-regulated genes, including Chrebp and Transketolase, which constitute a positive feedback loop in the regulation of Chrebp gene expression. Adenoviral overexpression of dnMlx in 25-week-old male C57BL/6J mice reduced hepatic triglyceride contents and improved glucose intolerance by inhibiting expression of Glucose-6-phosphatase and Elovl6 mRNA in addition to lipogenic enzymes. In conclusion, overexpression of dnMlx improves glucose intolerance by inhibiting expression not only of lipogenic enzymes but also other important genes such as Glucose-6-phosphatase and Elovl6.
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U2 - 10.1016/j.bbrc.2008.12.100
DO - 10.1016/j.bbrc.2008.12.100
M3 - Article
C2 - 19121288
AN - SCOPUS:58149502922
SN - 0006-291X
VL - 379
SP - 499
EP - 504
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -
