A high-fat diet increases interleukin-3 and granulocyte colony-stimulating factor production by bone marrow cells and triggers bone marrow hyperplasia and neutrophilia in wistar rats

Abstract

It is well established that the excessive consumption of a high-fat diet (HFD) results in overweight, obesity and an increase in leptin concentrations, which triggers a chronic inflammatory condition that is associated with a high white blood cell count. Two-month-old male Wistar rats were fed a control (CON) diet or an HFD for 12 weeks. After this period, hemogram, myelogram and biochemical parameters were evaluated along with the cell cycle and the percentage of CD34(+) cells in the bone marrow as well as cell proliferation and differentiation assays and the production of stem cell factor, interleukin 3 (IL-3), granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF). The HFD animals exhibited leukocytosis and neutrophilia with increased C-reactive protein, leptin, cholesterol and triglyceride concentrations. In the HFD group, the bone marrow revealed myeloid hyperplasia, especially of the granulocytic compartment with a higher percentage of CD34(+) cells and a higher percentage of cells in the G2/S/M cell cycle phases. In addition, the HFD bone marrow cells had a higher capacity to proliferate and differentiate into granulocytic cells in an in vitro system and a higher capacity to produce IL-3 and G-CSF. These data led us to infer that the HFD induces leukocytosis and neutrophilia suggesting alterations in hematopoiesis system modulation.

Immuno-metabolism and adipose tissue: The key role of hematopoietic stem cells

“…Both rapid dysregulation of B-cell populations that results from diminished cellular differentiation [61] and enhancement of hematopoiesis and lymphopoiesis [62] are reported, but these studies differ by the diet protocol. Consistent with data on ob/ob mice, leukocytosis and neutrophilia have also been described in HFD-rodents together with a granulopoiesis in the BM due to an increase in G-CSF production by stromal cells [60,63,64].…”

Sex-specific Relationships Between Il-3, Il-7 and Lipids in African Americans

“…Male Wistar rats fed an HFD for 12 weeks. exhibited leukocytosis and neutrophilia with increased CRP, leptin, cholesterol and TG concentrations [8]. In addition, the HFD bone marrow cells had a higher capacity to proliferate and differentiate into granulocytic cells which produce IL-3.…”

“…A previous study indicated that an HFD induced central and peripheral high leukocyte count and circulating neutrophils levels in rats [8]. The HFD animals had a higher number of bone marrow cells, which had a greater capacity to produce IL-3 and G-CSF [8]. It appears that HFD has an indirect effect on the levels of IL-3.…”

“…The β common chain family of cytokines regulate various in ammatory responses that promote the rapid clearance of pathogens but also contribute to pathology in chronic in ammation. A previous study indicated that an HFD induced central and peripheral high leukocyte count and circulating neutrophils levels in rats [8]. The HFD animals had a higher number of bone marrow cells, which had a greater capacity to produce IL-3 and G-CSF [8].…”

Obesity and inflammation and the effect on the hematopoietic system

“…One possible mechanism postulated to explain the augment in granulopoiesis is an increased production of G-CSF by bone marrow cells in the obese group compared to controls 23 . Moreover, mesenchymal stem cells (MSC) of HFD rats express considerably higher amounts of nuclear Factor kappa β (NF-kβ) as well as tumor necrosis factor alpha (TNFα), IL-1 and IL-6, which can inhibit adipocyte differentiation of MSC thus shifting bone marrow differentiation towards osteoblasts.…”