IER3 Promotes Expansion of Adipose Progenitor Cells in Response to Changes in Distinct Microenvironmental Effectors

Ravaud, Christophe; Estève, David; Villageois, Phi; Bouloumié, Anne; Dani, Christian; Ladoux, Annie

doi:10.1002/stem.2016

Cited by 8 publications

(17 citation statements)

References 52 publications

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“…In addition, from RNA interference experiments with siRNAs to IER3 that were previously validated 7 , we observed that EGR1 expression was dependent on IER3 expression (Fig. 5G), indicating that LPV may alter IER3 prior to EGR1 .…”

Section: Resultssupporting

confidence: 52%

“…We measured the ERK1/2 phosphorylation in response to activin A which is essential to maintain APs (hMADS) self-renewal 7, 8 .…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we focused on activin A and its crucial role to maintain self-renewal in adipose progenitors 7, 8 . We pointed out that activin A was involved in the preservation of AP pools by coordinating the balance between self-renewal and differentiation in an autocrine manner 7, 8 .…”

Section: Discussionmentioning

confidence: 99%

“…As AP cells need to perpetuate all life long, this pool is located in niches that maintain their intrinsic properties and control the self-renewal throughout adult life. Many factors present in the adipose tissue microenvironment are involved in a proper regulation of the balance between self-renewal and differentiation of these cells, including activin A which maintains the AP pool through autocrine and paracrine mechanisms 7, 8 . In addition, we recently identified the immediate early response 3 ( IER3 ) 9 as an important gene to control the activin A-induced expansion of this pool of cells 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Many factors present in the adipose tissue microenvironment are involved in a proper regulation of the balance between self-renewal and differentiation of these cells, including activin A which maintains the AP pool through autocrine and paracrine mechanisms 7, 8 . In addition, we recently identified the immediate early response 3 ( IER3 ) 9 as an important gene to control the activin A-induced expansion of this pool of cells 7 . IER3 is induced in response to distinct microenvironmental effectors that are susceptible to be modulated by therapeutic treatments.…”

Section: Introductionmentioning

confidence: 99%

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Impairment of the activin A autocrine loop by lopinavir reduces self-renewal of distinct human adipose progenitors

Ravaud¹,

Paré²,

Azoulay³

et al. 2017

Sci Rep

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Maintenance of the adipose tissue requires a proper balance between self-renewal and differentiation of adipose progenitors (AP). Any deregulation leads either to fat overexpansion and obesity or fat loss and consequent lipodystrophies. Depending on the fat pad location, APs and adipocytes are heterogeneous. However, information on the pharmacological sensitivity of distinct APs to drugs known to alter the function of adipose tissue, especially HIV protease inhibitors (PIs) is scant. Here we show that PIs decreased proliferation and clonal expansion of APs, modifying their self-renewal potential. Lopinavir was the most potent PI tested. Decrease in self-renewal was accompanied by a reduced expression of the immediate early response gene IER3, a gene associated with tissue expansion. It was more pronounced in chin-derived APs than in knee-derived APs. Furthermore, lopinavir lowered the activin A–induced ERK1/2 phosphorylation. Expressions of the transcription factor EGR1 and its targets, including INHBA were subsequently altered. Therefore, activin A secretion was reduced leading to a dramatic impairment of APs self-renewal sustained by the activin A autocrine loop. All together, these observations highlight the activin A autocrine loop as a crucial effector to maintain APs self-renewal. Targeting this pathway by HIV-PIs may participate in the induction of unwanted side effects.

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Section: Resultssupporting

confidence: 52%

“…We measured the ERK1/2 phosphorylation in response to activin A which is essential to maintain APs (hMADS) self-renewal 7, 8 .…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Impairment of the activin A autocrine loop by lopinavir reduces self-renewal of distinct human adipose progenitors

Ravaud¹,

Paré²,

Azoulay³

et al. 2017

Sci Rep

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Resveratrol and HIV‐protease inhibitors control UCP1 expression through opposite effects on p38 MAPK phosphorylation in human adipocytes

Ravaud

Paré

Yao

et al. 2019

Journal Cellular Physiology

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Brown and brown-like adipocytes (BBAs) control thermogenesis and are detected in adult humans. They express UCP1, which transforms energy into heat. They appear as promising cells to fight obesity. Deciphering the molecular mechanisms leading to the browning of human white adipocytes or the whitening of BBAs represents a goal to properly and safely control the pathways involved in these processes.Here, we analyzed how drugs endowed with therapeutic potential affect the differentiation of human adipose progenitor-cells into BBAs and/or their phenotype. We showed that HIV-protease inhibitors (PI) reduced UCP1 expression in BBAs modifying their metabolic profile and the mitochondria functionality.Lopinavir (LPV) was more potent than darunavir (DRV), a last PI generation. PPARγ and PGC-1α were decreased in a PI or cell-specific manner, thus altering UCP1's constitutive expression.In addition, LPV altered p38 MAPK phosphorylation, blunting then the β-adrenergic responses. In contrast, low doses of resveratrol stimulated the activatable expression of UCP1 in a p38 MAPK-dependent manner and counteracted the LPV induced loss of UCP1. This effect was independent of the resveratrol-induced sirtuin-1 expression.Altogether our results uncover how drugs impact crucial components of the networks regulating the expression of the thermogenic signature. They provide important information to control the relevant pathways involved in energy expenditure. K E Y W O R D Sadipose tissue, aging, brown adipocytes, energy metabolism, HIV protease inhibitors, p38 mitogen-activated kinase, resveratrol, sirtuin-1, UCP1, white adipocytes

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Circadian transcriptome oscillations in human adipose tissue depend on napping status and link to metabolic and inflammatory pathways

Rodríguez-Martín,

Pérez-Sanz,

Zambrano

et al. 2024

Sleep

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Study objectives Napping is a common habit in many countries. Nevertheless, studies about the chronic effects of napping on obesity are contradictory, and the molecular link between napping and metabolic alterations has yet to be studied. We aim to identify molecular mechanisms in adipose tissue (AT) that may connect napping and abdominal obesity. Methods In this cross-sectional study, we extracted the RNA repeatedly across 24h from cultured AT explants and performed RNA sequencing. Circadian rhythms were analyzed using 6 consecutive time points across 24 hours. We also assessed global gene expression in each group (nappers vs. non-nappers). Results With napping, there was a loss of rhythmicity in 88% of genes that showed circadian rhythmicity among non-nappers, a reduction in rhythm amplitudes of 29%, and significant phase changes from a coherent unimodal acrophase in non-nappers, towards a scattered and bimodal acrophase in nappers. Those genes that lost rhythmicity with napping were mainly involved in pathways of glucose and lipid metabolism, and of the circadian clock. Additionally, we found differential global gene expression between nappers and non-nappers with 34 genes down- and 32 genes up-regulated in nappers. The top up-regulated gene (IER3) and top down-regulated pseudogene (VDAC2P2) in nappers have been previously shown to be involved in inflammation Conclusion These new findings may have implications for our understanding of napping's effects on obesity and metabolic disorders.

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IER3 Promotes Expansion of Adipose Progenitor Cells in Response to Changes in Distinct Microenvironmental Effectors

Cited by 8 publications

References 52 publications

Impairment of the activin A autocrine loop by lopinavir reduces self-renewal of distinct human adipose progenitors

Impairment of the activin A autocrine loop by lopinavir reduces self-renewal of distinct human adipose progenitors

Resveratrol and HIV‐protease inhibitors control UCP1 expression through opposite effects on p38 MAPK phosphorylation in human adipocytes

Circadian transcriptome oscillations in human adipose tissue depend on napping status and link to metabolic and inflammatory pathways

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