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Nutrient-Gene Interactions

Hepatic Genes Altered in Expression by Food Restriction Are Not Influenced by the Low Plasma Glucose Level in Young Male GLUT4 Transgenic Mice^1,2

Chunxiao Fu^*, Liang Xi^*, Yimin Wu, Roger McCarter, Arlan Richardson^**,, Morgen Hickey^* and Eun-Soo Han^*,3

^* Department of Biological Science, University of Tulsa, 600 S. College Avenue, Tulsa, OK 74104; Department of Physiology and ^** Department of Cellular and Structural Biology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229; and South Texas Veterans Health Care System at San Antonio, San Antonio, TX 78229

³To whom correspondence should be addressed. E-mail: eun-han{at}utulsa.edu.

Because food restriction (FR) has a profound effect on most tissues, it is plausible that the modulation of aging by FR occurs through cellular processes such as gene expression. The effect of FR in lowering plasma glucose levels has been demonstrated in mice, rats, and nonhuman primates. The consistency of this finding suggests that decreased plasma glucose may be an important consequence of FR. Indeed, lowering plasma glucose in the absence of FR would be expected to change the expression of some of the same genes as seen with FR. GLUT4 transgenic (TG) mice were particularly suited to this examination because they have low plasma glucose levels like FR mice. We investigated altered gene expression by FR and the effect of low plasma glucose levels caused by genetic manipulation by measuring mRNA expression in liver tissues of 4- to 6-mo-old mice with 2.5–4.5 mo of FR using microarrays and 4 groups: GLUT4 TG (C57BL/6 background) consumed food ad libitum (AL), GLUT4 TG FR, wild-type littermates AL, and wild-type littermates FR. The 3 statistical analysis methods commonly indicated that FR altered the expression of 1277 genes; however, none of these genes was altered by additional GLUT4 expression. In fact, the low plasma glucose level in GLUT4 TG mice did not affect gene expression. Some results were confirmed by real-time quantitative RT-PCR. We conclude that a low plasma glucose level does not contribute to or coincide with the effect of FR on gene expression in the liver.

KEY WORDS: • gene expression • food restriction • GLUT4 transgenic mouse • GeneChip array

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