Vitamin A exerts its activity at the transcriptional level in the small intestine

The aim of this study was to examine the effects of vitamin-A deficiency on the small intestinal morphology and on brush-border enzyme function and expression. Methods: Weanling male rats were fed a vitamin-A deficient (VAD), sufficient (VAS), or supplemented (VASUP) diet, or were pair-fed (PF) with the VAD rats. Average food intakes were not different among the groups. Results: From days 35 to 42, the body weight of VAD rats began to plateau, whereas the other groups, including the PF rats, continued to gain weight. At days 48 to 51, the final mean body weight of VAD rats was significantly lower than that of PF, VAS and VASUP rats (P < 0.05). Serum and liver retinol levels were lower in VAD rats (by 85% and 99%, respectively) and higher in the VASUP group (by 126% and 160%, respectively) compared to the VAS group (P < 0.01). Histological examination of the jejunum revealed that in VAD rats the villi were shorter and thicker and there was an elevation in crypt depth relative to the other treatment groups. Infiltration of inflammatory cells was also observed in the jejunum of most of the VAD rats, but not in rats from other groups. Biochemical assays revealed that in VAD rats, alkaline phosphatase (ALP) and sucrase-isomaltase (SI) activities are significantly decreased in the jejunum, compared to PF, VAS and VASUP groups (P < 0.01). ALP activity was decreased in the duodenum of VAD rats as well. By comparison, amino-peptidase (AP) activity per mg protein in the jejunum and ileum of VAD rats was significantly increased compared to VAS and VASUP rats (P < 0.01), but was not different from PF rats. In all of the small intestinal sections, mRNA expression of all three brush-border enzymes relative to β-actin were significantly lower in VAD rats than in the other treatment groups. SI was similarly expressed in all of the small intestinal organs, whereas AP and ALP expression varied. Conclusions: Our results suggest that vitamin-A deficiency modifies the maturation and differentiation processes of the small intestinal mucosa at the transcriptional and post-transcriptional levels respectively. This in turn may be one explanation for the alteration or elimination of nutrient digestion and absorption during VAD.