Abstract

Adequate protein nutrition is essential for good health. Effects of protein malnutrition in animals have been widely studied at the mRNA level with the development of DNA microarray technology. Although microRNAs (miRNAs) have attracted attention for their function in regulating gene expression and have been studied in several disciplines, fewer studies have clarified the effects of protein malnutrition on miRNA alterations. The present study aimed to elucidate the relationship between protein malnutrition and miRNAs. Six-week old Wistar male rats were fed a control diet (20% casein) or a low-protein diet (5% casein) for two weeks, and their livers were subjected to both DNA microarray and miRNA array analysis. miR-203 was downregulated and its putative target Hadhb (hydroxyacyl-CoA dehydrogenase β subunit), known to regulate β-oxidation of fatty acids, was upregulated by the low-protein diet. In an in vitro experiment, miR-203 or its inhibitor were transfected in HepG2 cells, and the pattern of Hadhb expression was opposite to that of miR-203 expression. In addition, to clarifying the hepatic miRNA profile in response to protein malnutrition, these results showed that a low-protein diet increased Hadhb expression through downregulation of miR-203 and induced β-oxidation of fatty acids.

Highlights

  • As one of the three major nutrients, protein is essential for our lives, and adequate amounts and quality of protein intake are required to maintain good health

  • There were no significant differences in food intake between the two groups, growth retardation in the LP group was observed throughout the experimental period

  • It has been reported that dietary components affect biological functions through the It has been reported that dietary components affect biological functions through the modulation of miRNA expression

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Summary

Introduction

As one of the three major nutrients, protein is essential for our lives, and adequate amounts and quality of protein intake are required to maintain good health. The use of one type of omics analyses, transcriptomics, has rapidly proliferated owing to the development of DNA microarrays, which can detect the expression of large numbers of genes and is widely used in the discipline of nutritional research. Using these technologies, protein malnutrition has been shown to regulate the expression of many mRNAs. For example, Igf was found to be downregulated and Igfbp was found to be upregulated in rats fed a low-protein diet [5,6], which is considered to promote protein catabolism

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