The influence of protein, methionine, a crystalline amino acid mixture, oil or cellulose in the diet and the method used for diet sterilization on the fresh weight or total nitrogen (N) content of the cecum was examined in germ-free (GF) and conventional (CV) mice. These results showed that the fresh weight of the cecum in GF mice was much higher than that of CV mice fed the same diet, whereas the total N content of the cecum was less in GF mice than in CV mice. The cecum of mice given an amino acid mixture as the N source was lighter than that of mice given a purified whole-egg protein diet as the N source. The effect of the diets on shrinkage of the enlarged cecum in GF mice was insignificant compared with the action of several microbes in the gastrointestinal tract of CV mice.
Insulin-like growth factor-I (IGF-I) is an important growth factor for postnatal growth, and its plasma concentration is known to be regulated by nutrition. To investigate the mechanisms of regulation of IGF-I activity by IGF-I receptor (IGF-IR) and IGF-binding protein (IGFBP) under various nutritional conditions, the mRNA content and protein level of IGF-IR and IGFBP were studied with rats fed diets containing low amounts or a low nutritional quality of protein. The IGF-IR mRNA level and IGF binding activity in various tissues of the rats were not affected by dietary protein malnutrition. Among IGFBP-1-4, which are thought to be the main IGFBPs in plasma, the plasma IGFBP-1 concentration showed the greatest increase in response to dietary protein deprivation. The increased plasma IGFBP-1 level was accompanied by an increase in both liver mRNA content and the rate of transcription of its gene. Transient transfection analysis of deletion mutants demonstrated that the sequence -112--81 by 5′ to the transcription start site was responsible for the induction of IGFBP-1 gene transcription by dietary protein deprivation.
Dietary carbohydrates regulate the expression of genes involved in carbohydrate and lipid metabolism. Although this regulation may be mediated by insulin, there is a considerable amount of evidence indicating that carbohydrates or their metabolites, and not insulin itself, are directly involved in gene regulation. The L-type isozyme (LPK) gene of pyruvate kinase, an important glycolytic enzyme, is a good example. This gene is expressed in liver, kidney, small intestine, and pancreatic β-cells, and is stimulated by carbohydrates such as glucose and fructose at both the transcriptional and post-transcriptional levels. Two cis-acting regulatory elements named L-II and L-III are required for transcriptional stimulation of the LPK gene by carbohydrates. Although the L-III element is itself responsive to carbohydrates, L-II functions as an accessory element. Both nuclear factor 1 proteins and hepatocyte nuclear factor 4 bind to the L-II element. Further studies have suggested that the former is involved in carbohydrate stimulation of the LPK gene. However, the L-III element binding protein that is involved in carbohydrate regulation remains to be clarified. Available evidence suggests that the carbohydrate signaling pathway to the LPK gene includes a glucose metabolite, possibly glucose 6-phosphate or xylulose 5-phosphate, as well as phosphorylation and dephosphorylation mechanisms.