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Omics · study · 2026

Pericardial Adipose Tissue Regulates Cardiac Remodeling via Lipolysis-Mediated CD206+ Macrophage Expansion [snRNA-seq]

Listed in NCBI GEO

Obesity is a major risk factor for heart failure (HF).

Description

Recent clinical studies suggest an association between pericardial adipose tissue (PeAT) volume and HF, yet the underlying mechanisms remain elusive. Here, we demonstrate that impaired lipolysis in PeAT of obese mice exacerbates cardiac remodeling under pressure overload.

High-fat diet (HFD) feeding doubled PeAT volume in mice and accelerated cardiac fibrosis and dysfunction after transverse aortic constriction (TAC). PeAT removal prevented the cardiac remodeling in HFD mice, whereas PeAT transplantation from obese mice to lean mice recapitulated the adverse cardiac phenotype. In HFD mice, TGF-β1 was elevated in PeAT with increased downstream SMAD2 activation in adjacent myocardium.

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Single-nucleus transcriptomics identified CD206+ macrophages as the primary TGF-β1 source in PeAT from both HFD mice and HF patients. Three-dimensional imaging revealed sympathetic denervation in PeAT of obese mice, accompanied by impaired β3-adrenergic receptor-mediated lipolysis signaling, resulting in reduced local free fatty acid (FFA) availability that promoted CD206+ macrophage expansion. Intrapericardial TGF-β1 neutralization ameliorated cardiac remodeling in HFD mice, and further, restoring β3-adrenergic signaling in PeAT increased local FFA levels, suppressed SMAD2 activation in the heart, and improved cardiac function after TAC.

These findings establish a mechanistic link between PeAT dysfunction and HF progression in obesity, highlighting PeAT as a potential therapeutic target.

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Life Sciences
Inferred from text
Cardiac remodeling 75% · Heart 75% · Imaging 75% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 12 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE29560912 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[anatomy].local:anatomy:heartenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[disease].local:disease:cardiac-remodelingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:imagingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title