Extramedular Hematopoiesis in the Spleen of Obese Mice Modulation by the Alga Chlorella

Cristiane O Torello,Edgar J Paredes Gamero,Fernanda Martins

doi:10.4172/2167-0412.1000275

Abstract

In this study, Balb/C mice received standard or high-fat diet (HFD) and were treated with Chlorella for 5 days prior and 4 weeks after the onset of HFD. Our findings demonstrate that in HFD-induced obesity, there is a rapid decline in the number of granulocyte and macrophage progenitors (CFU-GM) in the bone marrow, which is associated with a continuous migration/increase of these cells into the spleen, a process characterized as extramedullary hematopoiesis (EMH). No changes in the size of the primitive (LSK), and reduction in the size of the granulocyte/macrophage (GMP) hematopoietic populations in the bone marrow were observed. We also found that increased expression of C-C chemokine receptor type 2 (CCR2) on GMP in the spleen might be a mechanism related to the migration of CFU-GM to this organ. Increased serum colony-stimulating activity (CSA) was also found in obese mice. IL-6 serum levels, measured at the end of the treatment (12 weeks) when impaired glucose tolerance was already established (Vecina et al.), was increased. Treatment with Chlorella restored to normal values the numbers of CFU-GM in the marrow and spleen, the percentage of GMP in the marrow, the expression of CCR2 on spleen GMP, the increased serum levels of IL-6, and further increased CSA compared to obese mice. These findings suggest the ability of Chlorella to modulate the shift in hematopoietic topographical hierarchy, probably due its anti-inflammatory properties.

Highlights

Obesity is a worldwide epidemic that results in enormous costs to health-care systems [1,2]
We demonstrate that in high-fat diet (HFD)-induced obesity, the rapid decline in the number of CFU-GM in the bone marrow is associated with a continuous migration of these cells into the spleen, which is characterized as extramedullary hematopoiesis (EMH)
In these two experimental models, the ability of the algae to produce cure or prolong survival was related to the degree of reversion of both myelosuppression and the increased EMH, reinforcing the assumption that this modulating effect of the algae is relevant to its therapeutic activity. Another important observation in this obesity model was the increased serum colony-stimulating activity (CSA), in spite of the reduced marrow CFU-GM numbers. These data corroborate our earlier reports in tumorbearing mice [9,11,16,32,47], and this effect has been interpreted as a consequence of the activity of suppressor cells, macrophages, in the spleen of these animals [48]

Summary

Introduction

Obesity is a worldwide epidemic that results in enormous costs to health-care systems [1,2]. A hallmark of inflammation in obesity is the accumulation and expansion of visceral adipose tissue (VAT) macrophages with an inflammatory phenotype, which, along with the decrease in anti-inflammatory T-regulatory cells in the VAT, results in an imbalanced environment and is thought to drive IR and the progression to T2D in obese subjects [4]. An important aspect observed during chronic inflammatory states is the appearance of extramedullary hematopoiesis (EMH), which consists in the ability of marrow cells to home, proliferate, and mature in extramedullary organs of adult animals. This involves pathophysiologic alterations in the stem cells and their microenvironment, enveloping extracellular matrix and stromal cells, in addition to local and systemic chemokine production [6]. Of importance here are our previous studies showing the relevance of the restoration of both the myelosuppression and the increased splenic EMH for recovering the homeostatic balance in the immunocompromised host, as observed during chronic inflammatory states such as infection and tumors [7,8,9,10,11,12,13,14,15,16]

Objectives

Methods

Results

Conclusion