Brucella abortus Infection Modulates 3T3-L1 Adipocyte Inflammatory Response and Inhibits Adipogenesis

Viglietti, Ayelén Ivana Pesce; Giambartolomei, Guillermo H.; Quarleri, Jorge; Delpino, M. Victoria

doi:10.3389/fendo.2020.585923

Cited by 7 publications

(9 citation statements)

References 78 publications

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“…Moreover, in line with the suggested role of TNFα as a key mediator of the effects induced by inflammation on preadipocytes and adipocyte differentiation [ 53 , 54 ], herein we reported TNFα—known to inhibit PPARγ activity through distinct mechanisms [ 21 , 22 ]—as a major pro-inflammatory cytokine able to alter PPARG splicing pattern. Ex vivo analyses on SAT biopsies revealed higher TNFA expression and a positive correlation with PPARGΔ5 levels only in obese (but not in lean) individuals, further supporting also in human hypertrophic adipocytes the link between inflammation and PPARG splicing alteration.…”

Section: Discussionsupporting

confidence: 81%

TNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells

Cataldi

Aprile

Melillo

et al. 2021

Cells

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Low-grade chronic inflammation and reduced differentiation capacity are hallmarks of hypertrophic adipose tissue (AT) and key contributors of insulin resistance. We identified PPARGΔ5 as a dominant-negative splicing isoform overexpressed in the AT of obese/diabetic patients able to impair adipocyte differentiation and PPARγ activity in hypertrophic adipocytes. Herein, we investigate the impact of macrophage-secreted pro-inflammatory factors on PPARG splicing, focusing on PPARGΔ5. We report that the epididymal AT of LPS-treated mice displays increased PpargΔ5/cPparg ratio and reduced expression of Pparg-regulated genes. Interestingly, pro-inflammatory factors secreted from murine and human pro-inflammatory macrophages enhance the PPARGΔ5/cPPARG ratio in exposed adipogenic precursors. TNFα is identified herein as factor able to alter PPARG splicing—increasing PPARGΔ5/cPPARG ratio—through PI3K/Akt signaling and SRp40 splicing factor. In line with in vitro data, TNFA expression is higher in the SAT of obese (vs. lean) patients and positively correlates with PPARGΔ5 levels. In conclusion, our results indicate that inflammatory factors secreted by metabolically-activated macrophages are potent stimuli that modulate the expression and splicing of PPARG. The resulting imbalance between canonical and dominant negative isoforms may crucially contribute to impair PPARγ activity in hypertrophic AT, exacerbating the defective adipogenic capacity of precursor cells.

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Section: Discussionsupporting

confidence: 81%

TNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells

Cataldi

Aprile

Melillo

et al. 2021

Cells

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“…Among these, IL-6 could exacerbate bone loss through the inhibition of osteoblast differentiation [ 31 ]. As we have demonstrated, B. abortus -infected adipocytes secrete IL-6 [ 25 ] ( Figure 2 A). Additionally, IL-6 was secreted by osteoblasts stimulated with culture supernatants from B. abortus -infected adipocytes, while supernatants from non-infected adipocytes had no effect.…”

Section: Resultsmentioning

confidence: 74%

“…Both cytokines could be secreted by adipocytes. However, we demonstrated that IL-6 is secreted by B. abortus -infected adipocytes [ 25 ]. The consequence of IL-6 on osteoblast differentiation previously demonstrated that IL-6 inhibits the expression of Runx2 and Osterix (Osx) with concomitant inhibition of matrix mineralization [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…We have already reported that B. abortus can infect and survive in osteoblasts and adipocytes and that this infection induces the expression of proinflammatory cytokines, matrix metalloproteases and chemokines, which could be implicated in the osteoarticular manifestations of brucellosis [ 25 , 27 , 28 ]. Here, we investigate the crosstalk between B. abortus -infected osteoblasts and adipocytes and the incumbency of soluble mediators produced by each of these in the modulation of precursor cell differentiation.…”

Section: Introductionmentioning

confidence: 99%

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B. abortus Infection Promotes an Imbalance in the Adipocyte–Osteoblast Crosstalk Favoring Bone Resorption

Freiberger

López

Sviercz

et al. 2023

IJMS

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Osteoarticular injury is the most common presentation of active brucellosis in humans. Osteoblasts and adipocytes originate from mesenchymal stem cells (MSC). Since those osteoblasts are bone-forming cells, the predilection of MSC to differentiate into adipocytes or osteoblasts is a potential factor involved in bone loss. In addition, osteoblasts and adipocytes can be converted into each other according to the surrounding microenvironment. Here, we study the incumbency of B. abortus infection in the crosstalk between adipocytes and osteoblasts during differentiation from its precursors. Our results indicate that soluble mediators present in culture supernatants from B. abotus-infected adipocytes inhibit osteoblast mineral matrix deposition in a mechanism dependent on the presence of IL-6 with the concomitant reduction of Runt-related transcription factor 2 (RUNX-2) transcription, but without altering organic matrix deposition and inducing nuclear receptor activator ligand kβ (RANKL) expression. Secondly, B. abortus-infected osteoblasts stimulate adipocyte differentiation with the induction of peroxisome proliferator-activated receptor γ (PPAR-γ) and CCAAT enhancer binding protein β (C/EBP-β). We conclude that adipocyte–osteoblast crosstalk during B. abortus infection could modulate mutual differentiation from its precursor cells, contributing to bone resorption.

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“…One report in 2018 described the presence of B. canis in fat cells of the gastro-splenic ligament, next to lipid droplets and precisely where ER is located, in naturally infected fetuses and neonates [ 149 ]. More recently, B. abortus has been shown to replicate in a murine fibroblastic derived adipocyte-like cell line, the 3T3-L1 cells, and in its differentiated adipocyte derivative, albeit with less efficiency [ 150 ]. However, in this system, bacterial loads start to decline steadily from 3 days p.i.…”

Section: Reservoirsmentioning

confidence: 99%

Brucella: Reservoirs and Niches in Animals and Humans

et al. 2021

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Brucella is an intracellular bacterium that causes abortion, reproduction failure in livestock and leads to a debilitating flu-like illness with serious chronic complications if untreated in humans. As a successful intracellular pathogen, Brucella has developed strategies to avoid recognition by the immune system of the host and promote its survival and replication. In vivo, Brucellae reside mostly within phagocytes and other cells including trophoblasts, where they establish a preferred replicative niche inside the endoplasmic reticulum. This process is central as it gives Brucella the ability to maintain replicating-surviving cycles for long periods of time, even at low bacterial numbers, in its cellular niches. In this review, we propose that Brucella takes advantage of the environment provided by the cellular niches in which it resides to generate reservoirs and disseminate to other organs. We will discuss how the favored cellular niches for Brucella infection in the host give rise to anatomical reservoirs that may lead to chronic infections or persistence in asymptomatic subjects, and which may be considered as a threat for further contamination. A special emphasis will be put on bone marrow, lymph nodes, reproductive and for the first time adipose tissues, as well as wildlife reservoirs.

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Brucella abortus Infection Modulates 3T3-L1 Adipocyte Inflammatory Response and Inhibits Adipogenesis

Cited by 7 publications

References 78 publications

TNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells

TNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells

B. abortus Infection Promotes an Imbalance in the Adipocyte–Osteoblast Crosstalk Favoring Bone Resorption

Brucella: Reservoirs and Niches in Animals and Humans

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