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BAFF neutralization impairs the clearance of dead adipocytes and promotes insulin resistance in obese mice

ABSTRACT: BAFF neutralization impairs the clearance of dead adipocytes and promotes insulin resistance in obese mice

PROVIDER: PRJNA1077285 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27989353_1.fastq.gz	Fastqsanger.gz
	SRR27989353_2.fastq.gz	Fastqsanger.gz
	SRR27989354_1.fastq.gz	Fastqsanger.gz
	SRR27989354_2.fastq.gz	Fastqsanger.gz
	SRR27989355_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

BAFF neutralization impairs the clearance of dead adipocytes and promotes insulin resistance in obese mice

Project description:B cell-activating factor (BAFF) is critical for the survival and maturation of B2 cells. However, excess BAFF breaks the peripheral tolerance of B2-cells leading to the production of autoantibodies that cause autoimmune diseases. During obesity, BAFF is predominantly produced by white adipose tissue (WAT), and IgG autoantibodies against adipocytes are identified in the WAT of obese humans. However, it remains to be determined if the autoantibodies formed during obesity affect WAT remodeling and systemic insulin resistance. Here, we show that IgGs from high-fat diet (HFD)-induced obese mice bind to apoptotic adipocytes and promote their clearance by macrophages. Next, using murine models of obesity in which the gonadal WAT undergoes remodeling, unexpectedly we found that BAFF neutralization increased the number of dead adipocytes and exacerbated WAT inflammation and insulin resistance despite depletion of IgG autoantibodies. RNA sequencing of the stromal vascular fraction from the WAT revealed impaired B cell activation and phagocytosis pathways. In-vitro, the clearance of apoptotic adipocytes by macrophages was attenuated in the presence of IgGs from BAFF-neutralized mice compared to the control mice. Altogether, our study suggests a beneficial role of BAFF and IgG autoantibodies in WAT remodeling in obesity and the regulation of systemic insulin resistance.

2024-08-28 | GSE255950 | GEO

BAFF neutralization impairs the autoantibody-mediated clearance of dead adipocytes and aggravates obesity-induced insulin resistance.

Project description:B cell-activating factor (BAFF) is a critical TNF-family cytokine that regulates homeostasis and peripheral tolerance of B2 cells. BAFF overproduction promotes autoantibody generation and autoimmune diseases. During obesity, BAFF is predominantly produced by white adipose tissue (WAT), and IgG autoantibodies against adipocytes are identified in the WAT of obese humans. However, it remains to be determined if the autoantibodies formed during obesity affect WAT remodeling and systemic insulin resistance. Here, we show that IgG autoantibodies are generated in high-fat diet (HFD)-induced obese mice that bind to apoptotic adipocytes and promote their phagocytosis by macrophages. Next, using murine models of obesity in which the gonadal WAT undergoes remodeling, we found that BAFF neutralization depleted IgG autoantibodies, increased the number of dead adipocytes, and exacerbated WAT inflammation and insulin resistance. RNA sequencing of the stromal vascular fraction from the WAT revealed decreased expression of immunoglobulin light-chain and heavy-chain variable genes suggesting a decreased repertoire of B cells after BAFF neutralization. Further, the B cell activation and the phagocytosis pathways were impaired in the WAT of BAFF-neutralized mice. In vitro, plasma IgG fractions from BAFF-neutralized mice reduced the phagocytic clearance of apoptotic adipocytes. Altogether, our study suggests that IgG autoantibodies developed during obesity, at least in part, dampens exacerbated WAT inflammation and systemic insulin resistance.

| S-EPMC11341376 | biostudies-literature

Lysosomal exocytosis by macrophages as a druggable mechanism for anti-inflammatory clearance of dead adipocytes in adipose tissue

Project description:The clearance of dead adipocytes in adipose tissue (AT) poses a major challenge due to their large size, which exceeds the phagocytic capacity of macrophages and prevents classical, anti-inflammatory efferocytosis. Instead, adipose tissue macrophages (ATMs) accumulate around dying adipocytes, forming crown-like structures (CLS), and engage in lysosomal exocytosis – the extracellular degradation of adipocytes. In this study, we used an ex vivo explant model of murine epididymal white AT, cultured over seven days to investigate pharmacological strategies that modulate lysosomal exocytosis. We observed a progressive increase in CLS formation, secretion of the lysosomal enzymes ß-Hexosaminidase A (HEXA) and lysosomal acid lipase (LAL), and surface abundance of LAMP1 and LAMP2, confirming ATMs as key mediators of this process. Notably, activation of lysosomal exocytosis with the mTOR inhibitor Rapamycin enhanced adipocyte clearance and significantly reduced inflammatory ATM abundance and TNF-α secretion. Bulk RNA sequencing of ATMs revealed a highly significant impact of Rapamyin on ATM proliferation. In contrast, inhibition of lysosomal exocytosis with PIKfyve inhibitor Apilimod or targeted inhibition of LAL using Lalistat-2 disrupted lysosomal function and promoted a pro-inflammatory ATM phenotype. Our findings highlight lysosomal exocytosis as a critical pathway for the resolution of dead adipocytes and the regulation of inflammation in adipose tissue. Pharmacological enhancement of this process may represent a promising therapeutic approach to attenuate inflammation in AT and its metabolic consequences, including insulin resistance and type 2 diabetes.

2025-09-03 | GSE307090 | GEO

Stem cells tightly regulate dead cell clearance to maintain tissue fitness

Project description:Stem cells tightly regulate dead cell clearance to maintain tissue fitness

| PRJNA1129187 | ENA

Delta4-BAFF an new transcription factor

Project description:The purpose of the study was to identify downstream gene targets regulated by a new alternative splice of BAFF (B-Cell Activating factor belonging to the TNF Family) that we called Delta4-BAFF (because it characterized by an alternative splice of exon 4). To do this we used human burkitt's lymphoma cell line (RAMOS) stably transfected with Delta4-BAFF or stably transfected with Delta4-BAFF mutated on its N-glycosylation site (Delta4-BAFF-N124D). One control was used : RAMOS stably transfected with empty vector (pIRES2-GFP from Clontech)

2012-09-28 | E-MEXP-3595 | biostudies-arrayexpress

DEAD

Project description:DEAD

| PRJEB12645 | ENA

Stem cells tightly regulate dead cell clearance to maintain tissue fitness [scRNA-seq]

Project description:Stem cells tightly regulate dead cell clearance to maintain tissue fitness [scRNA-seq]

| PRJNA1129850 | ENA

Stem cells tightly regulate dead cell clearance to maintain tissue fitness [ATAC-seq]

Project description:Stem cells tightly regulate dead cell clearance to maintain tissue fitness [ATAC-seq]

| PRJNA1129188 | ENA

Stem cells tightly regulate dead cell clearance to maintain tissue fitness [CUT&Run]

Project description:Stem cells tightly regulate dead cell clearance to maintain tissue fitness [CUT&Run]

| PRJNA1129097 | ENA

Lysosomal exocytosis by macrophages as a druggable mechanism for anti-inflammatory clearance of dead adipocytes in adipose tissue

Project description:Lysosomal exocytosis by macrophages as a druggable mechanism for anti-inflammatory clearance of dead adipocytes in adipose tissue

| PRJNA1314244 | ENA

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