Obesity-induced inflammation: The impact of the hematopoietic stem cell niche
Emily Bowers, Kanakadurga Singer
Emily Bowers, Kanakadurga Singer
Published February 8, 2021
Citation Information: JCI Insight. 2021;6(3):e145295. https://doi.org/10.1172/jci.insight.145295.
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Review

Obesity-induced inflammation: The impact of the hematopoietic stem cell niche

Abstract

Obesity and obesity-related diseases like type 2 diabetes (T2D) are prominent global health issues; therefore, there is a need to better understand the mechanisms underlying these conditions. The onset of obesity is characterized by accumulation of proinflammatory cells, including Ly6chi monocytes (which differentiate into proinflammatory macrophages) and neutrophils, in metabolic tissues. This shift toward chronic, low-grade inflammation is an obese-state hallmark and highly linked to metabolic disorders and other obesity comorbidities. The mechanisms that induce and maintain increased inflammatory myelopoiesis are of great interest, with a recent focus on how obesity affects more primitive hematopoietic cells. The hematopoietic system is constantly replenished by proper regulation of hematopoietic stem and progenitor (HSPC) pools in the BM. While early research suggests that chronic obesity promotes expansion of myeloid-skewed HSPCs, the involvement of the hematopoietic stem cell (HSC) niche in regulating obesity-induced myelopoiesis remains undefined. In this review, we explore the role of the multicellular HSC niche in hematopoiesis and inflammation, and the potential contribution of this niche to the hematopoietic response to obesity. This review further aims to summarize the potential HSC niche involvement as a target of obesity-induced inflammation and a driver of obesity-induced myelopoiesis.

Authors

Emily Bowers, Kanakadurga Singer

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Figure 1

Obesity-induced alterations of the BM and HSC niche influence hematopoiesis.

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Obesity-induced alterations of the BM and HSC niche influence hematopoie...
Hematopoiesis is tightly regulated by cytokines produced through the HSC niche, and research has begun to identify the individual contribution of each of these populations in the regulation and maintenance of the HSC pool (top panel). During obesity (bottom panel), the BM landscape changes dramatically. Increased production of leptin from expanding adipose tissue leads to biased differentiation of LepR+ perivascular cells toward adipogenesis at the expense of osteogenesis, leading to a significant loss of bone density. While the impact of this physical expansion of the BMAT on the rest of the HSC niche and hematopoiesis is not yet known, this increase would bring many more hematopoietic and stromal cells into direct and/or closer contact with BMAT. Additionally, the expanding AT leads to increased production of proinflammatory monocytes, macrophages, and neutrophils, which in turn leads to an increase in the basal levels of inflammatory cytokines. Chronic exposure to HFD also leads to increased levels of circulating free fatty acids, which could act on both stromal and hematopoietic cells to drive and sustain production of inflammatory myelopoiesis. Illustrated by Rachel Davidowitz.