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Dietary Energy Restriction in Mice Reduces Hepatic Expression of Glucose-Regulated Protein 78 (BiP) and 94 mRNA¹

Department of Biochemistry, University of California, Riverside, CA 92521 ^* Department of Pathology, School of Medicine, University of California, Los Angeles, CA 90024

The influence of life span-prolonging dietary energy restriction on hepatic expression of glucose-regulated protein 78 and 94 (GRP78 and GRP94) RNA was investigated in female C3B10RF₁ mice. Mice were either fed ad libitum or fed diets reduced 20 or 40% in energy but containing approximately equivalent amounts of protein, fats, vitamins and minerals. Aging produced no changes in GRP mRNA. However, GRP78 and GRP94 mRNA levels were reduced 50 and 40%, respectively, by 40% energy restriction. This level of energy restriction produced a 43% reduction in the mean plasma glucose levels of young and old mice. The changes in GRP mRNA expression appear to be specific, because the levels of these RNAs were normalized to the level of polyadenylated RNA, and no changes were detected in the levels of a number of other mRNAs. Although extreme glucose deprivation increases GRP mRNA levels in cultured cell lines, physiologically relevant reductions in blood glucose had the opposite effect in the liver, in vivo. The regulatory pathway responsible for these effects is not known. GRP mRNA levels are elevated by agents that increase the level of malfolded proteins in the endoplasmic reticulum. Thus, energy restriction may act to reduce malfolded proteins in the endoplasmic reticulum of hepatic cells.

KEY WORDS: • energy restriction • glucose-regulated protein • GRP mRNA • mouse • liver

¹ This research was supported by National Institutes of Health grants AG-04419 and AG-00424.

Manuscript received 29 January 1990. Revision accepted 10 May 1990.

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