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 | 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 [DBDB_singlecell]

2024-06-14 | GSE232277 | 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

Flattened circadian glucocorticoid oscillations cause obesity due to increased lipid turnover and lipid uptake

Project description:Chronic stressors flatten circadian glucocorticoid (GC) oscillations, which has been correlated with negative health outcomes including obesity. How such flattened circadian GC oscillations affect metabolism and fat storage remains unknown. Here we investigated the consequences in mice and found that flattening of GC oscillations results not only in body weight gain, mainly due to increases in white fat depot mass, but also leads to hyperinsulinemia and fat accumulation in brown adipose tissue. Global analysis of the transcriptome of WAT and BAT revealed alterations in gene expression dependent on flattened GC oscillations and point to increased lipid turnover and lipid uptake in both fat depots.

2022-05-13 | GSE202800 | GEO

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