Medical Student Research Fellowship for Summer 2005

Mentor: Kosaku Uyeda
Department: Biochemistry
Room number:
Mail Code: 9038
Phone number: 214-857-0318
E-mail: kuyeda6400@aol.com
Project title: Carbohydrate Regulation of Hepatic Gene Expression

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable): 0203-02-05-1

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Brief Description of Project:

The liver is the principal organ responsible for the conversion of excess dietary carbohydrate into triglycerides. Ingestion of high carbohydrate diet induces transcription of more than 15 genes involved in the metabolic conversion of glucose to storage fat. It has shown that nutrients themselves, in dependent of insulin, play an important role in the regulation of transcription. We are interested in elucidating the mechanism by which carbohydrate generates a signal induce the transcription and activation of lipogenic enzyme genes. Recently we have identified and characterized a new transcription factor termed "Carbohydrate response element binding protein, ChREBP" which responds to high carbohydrate and induce the liver enzyme genes. We have prepared ChREBP gene knockout mice and currently analyzing various genes affected by the mutation. We also prepared double cross mutant of ChREBP-KO and ob/ob mice to study the effect, and plan to study physiological,biochemical and metabolic changes in these mice.

Previous Research Activities or Publications with Medical Students:

Uyeda,K.,Yamashita, H., and Kawaguchi, K., (2002) Commentary. Carbohydrate Responsive Element Binding Protein (ChREBP): A key Regulator of Glucose Metabolism and Fat Storage. Biochem. Pharmacol. 7243, 1 - 6.
Kabashima, T., Kawaguchi, T., and Uyeda, K. (2003) Xylulose-5-phosaphate Activated Protein Phosphatase is Mechanism of Hepatic Glucose-induced Lipogenesis. Proc. Natl. Acad. Sci. USA 100, 5107-5112.
Jin, E. S., Uyeda, K., Kawaguchi, T., Burgess, S., Malloy, C. R., and Sherry, A. D. (2003) Increased hepatic fructose 2,6-bisphosphate after an oral glucose load does not affect gluconeogenesis. J. Biol Chem. 278, 28427-28433.
Uyeda, K. (2004) Pyruvate kinase. Encyclopedia of Biological Science Lennarz and M.D. Lane eds. Academic Press/Elsevier Science San Diego, CA. (in press)
Iizuka, K., Bruick, R.K., Liang, G., Horton, J.D., and Uyeda, K. (2004) Deficiency of carbohydrate response element binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc. Natl. Acad. Sci. USA 101, 7281-7286.
Ishii, S., Iizuka, K., Miller, B.C., and Uyeda, K. (2004) Carbohyrate response element binding protein directly promotes lipogenic enzyme gene transcription. Proc. Natl.,Acad. Sci. USA 101,

Return to UT Southwestern Homepage

Return to Student Research Projects Index