# Effect of a high-fat diet and iron overload on erythropoiesis in mice

## TL;DR

This study explores how a high-fat diet and iron overload affect red blood cell production in mice, revealing changes in reticulocyte populations and early erythroid precursors.

## Contribution

The study provides new insights into how hyperinsulinemia and iron overload independently and synergistically influence erythropoiesis in mice.

## Key findings

- HFD-fed wild-type mice had increased reticulocytes in the bone marrow compared to control diet-fed mice.
- Hamp1−/− mice showed higher hematological parameters and increased early erythroid precursors when fed HFD.
- Hyperinsulinemia and iron overload appear to independently influence erythroid differentiation in mice.

## Abstract

Insulin and iron availability stimulate and regulate erythropoiesis, respectively. The effects of hyperinsulinemia and/or iron overload on erythroid differentiation are unclear.

Male C57Bl/6J wild-type (WT) mice were fed a high-fat diet (HFD) (to produce hyperinsulinemia) or a control diet (CD) for varying periods (4–24 weeks). Hepcidin knock-out (Hamp1−/−) mice (which are iron-overloaded) were fed CD or HFD for 24 weeks. Terminal erythroid differentiation (TED) in the bone marrow (BM) from these mice was analyzed by flow cytometry. Hematological parameters were estimated in peripheral blood.

HFD-feeding of WT mice did not significantly affect erythroid precursors in the BM or hematological parameters. However, these mice had a significantly higher reticulocyte population in the BM than those fed CD (at all time points studied). Values of hematological parameters were higher in Hamp1−/− mice than WT mice, at 24 weeks of feeding (irrespective of diet type), indicating increased erythropoiesis. Early erythroid precursors in the BM were higher in HFD-fed Hamp1−/− mice than those fed CD.

HFD-feeding in WT mice resulted in increases in the proportion of reticulocytes in the bone marrow; maturation of the early erythroid precursors was not significantly affected. In Hamp1−/− mice, HFD-feeding increased the number of early erythroid precursors.

•The impact of hyperinsulinemia and iron overload on erythropoiesis is unclear.•Wild-type and hepcidin knockout mice were fed high-fat diet (HFD) or control diet.•Terminal erythroid maturation (TED) was assessed by flow cytometry.•HFD-feeding of wild-type mice resulted in increased reticulocytes in the bone marrow.•In Hamp1−/− mice, HFD-feeding increased the number of early erythroid precursors.

The impact of hyperinsulinemia and iron overload on erythropoiesis is unclear.

Wild-type and hepcidin knockout mice were fed high-fat diet (HFD) or control diet.

Terminal erythroid maturation (TED) was assessed by flow cytometry.

HFD-feeding of wild-type mice resulted in increased reticulocytes in the bone marrow.

In Hamp1−/− mice, HFD-feeding increased the number of early erythroid precursors.