Establishing a Rat Model of Intestinal Heme-iron Absorption

Heme iron, derived from hemoglobin and myoglobin of animal products, is efficiently absorbed and utilized by humans. Despite extensive investigation over the last several decades, the exact mechanism(s) of heme-iron absorption and tissue utilization of absorbed heme are unclear. Mice are frequently used for investigation of iron biology; however, mice do not efficiently utilize dietary iron derived from heme, so development of alternative models is warranted. Rats could more efficiently utilize dietary heme iron, but this has not been rigorously tested. Our initial studies demonstrated that dietary heme (derived from porcine RBCs) could partially correct iron-deficiency anemia (IDA) in rats of one strain (rat strain 1), but not in 2 others. We hypothesized that a heme-iron diet would fully replete strain 1 rats with IDA, at a similar rate to a non-heme iron (NHI) diet. We utilized repletion diets containing 50, 75 or 100 ppm heme iron; a control diet contained 50 ppm NHI. Forty-two, three-week-old, female strain 1 rats were weaned onto a low-iron diet with 3-4 ppm NHI, and then after 2 weeks, rats were repleted with the different diets for 8 days. Rats were housed in overhanging wire bottom stainless steel cages during the low-iron feeding period to prevent coprophagia. Blood was collected from the tail vein at baseline and every 4 days thereafter to track correction of anemia. Outcomes showed that repletion of IDA rats with the 50-ppm heme-iron diet resolved the anemia; however, tissue iron depletion indicated that the rats remained iron deficient. Also, the rate of repletion was slightly slower as compared to rats repleted with the control (50 ppm NHI) diet. With higher dietary heme-iron levels, repletion was as fast, or even faster, than in control rats suggesting that a rat strain was identified that can efficiently assimilate dietary heme iron. Our studies support a role for rats as a genetic model to preferentially mimic human nutritional studies of iron and heme absorption. This investigation was funded by grant DK074867 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (JFC, PI), and grant DK109717 from NIDDK and the Office of Dietary Supplements (to JFC, PI). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.