Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P56851 (
epididymal
)
11,273
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Adipose tissue (AT) fibrosis in obesity compromises adipocyte functions and responses to intervention-induced weight loss. It is driven by AT progenitors with dual fibro/adipogenic potential, but pro-fibrogenic pathways activated in obesity remain to be deciphered. To investigate the role of macroautophagy/autophagy in AT fibrogenesis, we used
Pdgfra-Cre
Ert2
transgenic mice to create conditional deletion of
Atg7
alleles in AT progenitor cells (
atg7
cKO) and examined sex-dependent, depot-specific AT remodeling in high-fat diet (HFD)-fed mice. Mice with
atg7
cKO had markedly decreased extracellular matrix (ECM) gene expression in visceral, subcutaneous, and epicardial adipose depots compared to
Atg7
lox/lox
littermates. ECM gene program regulation by autophagy inhibition occurred independently of changes in the mass of fat tissues or adipocyte numbers of specific depots, and cultured preadipocytes treated with pharmacological or siRNA-mediated autophagy disruptors could mimic these effects. We found that autophagy inhibition promotes global cell-autonomous remodeling of the paracrine TGF-BMP family landscape, whereas ECM gene modulation was independent of the autophagic regulation of
GTF2IRD1
. The progenitor-specific mouse model of ATG7 inhibition confirms the requirement of autophagy for white/beige adipocyte turnover, and combined to
in vitro
experiments, reveal progenitor autophagy dependence for AT fibrogenic response to HFD, through the paracrine remodeling of TGF-BMP factors balance.
Abbreviations:
CQ: chloroquine; ECM: extracellular matrix; EpiAT:
epididymal
adipose tissue;
GTF2IRD1
: general transcription factor II I repeat domain-containing 1; HFD: high-fat diet; KO: knockout; OvAT: ovarian adipose tissue; PDGFR: platelet derived growth factor receptor; ScAT: subcutaneous adipose tissue; TGF-BMP: transforming growth factor-bone morphogenic protein.
...
PMID:Autophagy inhibition blunts PDGFRA adipose progenitors' cell-autonomous fibrogenic response to high-fat diet. 3199 25
