Dietary protein upregulates fractional intestinal iron absorption and directly increases DMT1 transcript and protein expression

Iron (Fe) deficiency is endemic worldwide. We have recently found that increasing dietary protein dose‐dependently improves Fe balance in rats. This change is associated with increased DMT1 transcript expression, a key regulator of intestinocyte Fe uptake. To confirm the Fe balance results, Fe absorption studies were performed in rats fed either a 20% (control) or 40% (high) protein diet for 1 wk. Rats on the 40% protein diet absorbed 30±9% of ingested Fe while those on the 20% protein diet absorbed 18±8% ( p = 0.005). To determine if DMT1 protein expression is also increased with increasing dietary protein, Western analyses were undertaken using duodenal mucosal lysates prepared from rats on the 20% and 40% protein diets. There was a trend towards higher DMT1 protein levels on the 40% diet (1.7±1.1 fold; p =0.46). To evaluate if amino acids could directly increase DMT1 transcript expression, Caco‐2 Bbe cells were exposed to either a mixture of amino acids or amino acid‐free media for 6 hrs. Amino acid treatment induced DMT1 mRNA by 1.6±0.3 fold as determined by qPCR ( p< 0.02). These data indicate that increasing dietary protein increases intestinal Fe absorption in part by upregulation of DMT1. Further, there appears to be a direct effect of amino acids on DMT1 transcript expression. This work was supported by a HATCH grant from the Univ. of CT.