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Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity

ABSTRACT: Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity

PROVIDER: PRJNA971519 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24508017.fastq.gz	Fastqsanger.gz
	SRR24508018.fastq.gz	Fastqsanger.gz
	SRR24508019.fastq.gz	Fastqsanger.gz
	SRR24508020.fastq.gz	Fastqsanger.gz
	SRR24508021.fastq.gz	Fastqsanger.gz

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Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [ATGL_Bulk]

Project description:Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [ATGL_Bulk]

| PRJNA971523 | ENA

Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [CD36_Bulk]

Project description:Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [CD36_Bulk]

| PRJNA971524 | ENA

Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [DBDB_Bulk]

Project description:Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [DBDB_Bulk]

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Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [DBDB_singlecell]

Project description:Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [DBDB_singlecell]

| PRJNA971526 | ENA

Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [DBDB_singlecell]

Project description:Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity in mice and human, but the molecular mechanisms that drive BAT cell remodeling remain largely. Using a multilayered approach, we comprehensively map a deep reorganization in the BAT cells. We uncovered a subset of macrophages as the lipid-associated macrophages (LAM), which were massively increased in genetic and dietary model of BAT expansion. LAM participate in this scenario by capturing extracellular vesicles carrying damaged lipids and mitochondria released from metabolically-stressed brown adipocytes. CD36 scavenger receptor drives LAM phenotype and through * in vitro* and *in vivo* models, we demonstrated that CD36-deficient LAM increased brown fat genes. LAM release Tgfb1 that reduces brown adipocytes identity through Aldh1a1 induction. This study provides the first description of cell dynamics in BAT of obese models identifying LAM as responder to tissue-level metabolic stress and key driver to loss of BAT cell identity.

2024-06-14 | GSE232277 | GEO

Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [DBDB_Bulk]

2024-06-14 | GSE232276 | GEO

Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [CD36_Bulk]

2024-06-14 | GSE232275 | GEO

Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity [ATGL_Bulk]

2024-06-14 | GSE232274 | GEO

Lipid-Associated Macrophages Reshape BAT Cell Identity in Obesity

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-06-14 | GSE232278 | GEO

Vascular rarefaction mediates whitening of brown fat in obesity

Project description:Brown adipose tissue (BAT) is a highly vascularized organ with abundant mitochondria that produce heat through uncoupled respiration. Obesity is associated with a reduction of BAT function; however, it is unknown how obesity promotes dysfunctional BAT. Here, using a murine model of diet-induced obesity, we determined that obesity causes capillary rarefaction and functional hypoxia in BAT, leading to a BAT “whitening” phenotype that is characterized by mitochondrial dysfunction, lipid droplet accumulation, and decreased expression of Vegfa. Targeted deletion of Vegfa in adipose tissue of nonobese mice resulted in BAT whitening, supporting a role for decreased vascularity in obesity-associated BAT. Conversely, introduction of VEGF-A specifically into BAT of obese mice restored vascularity, ameliorated brown adipocyte dysfunction, and improved insulin sensitivity. The capillary rarefaction in BAT that was brought about by obesity or Vegfa ablation diminished β-adrenergic signaling, increased mitochondrial ROS production, and promoted mitophagy. These data indicate that overnutrition leads to the development of a hypoxic state in BAT, causing it to whiten through mitochondrial dysfunction and loss. Furthermore, these results link obesity-associated BAT whitening to impaired systemic glucose metabolism.

2024-12-18 | GSE221854 | GEO

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