Autophagy inhibition blunts PDGFRA adipose progenitors' cell-autonomous fibrogenic response to high-fat diet

Autor: Nadine Suffee, Geneviève Marcelin, Emmanuel L. Gautier, Amélie Lacombe, Carla Da Cunha, Isabelle Dugail, Christine Rouault, Nataliya Sokolovska, Karine Clément, Arnaud Leclerc, Camille Gamblin
Přispěvatelé: Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dugail, Isabelle, Instituts Hospitalo-Universitaires - Institut de Cardiologie-Métabolisme-Nutrition - - ICAN2010 - ANR-10-IAHU-0005 - IAHU - VALID, Appel à projets générique - LIPA, une nouvelle cible thérapeutique pour le traitement des maladies cardiométaboliques - - LIPOCAMD2014 - ANR-14-CE12-0017 - Appel à projets générique - VALID, Contrôler la fonction des progéniteurs du tissu adipeux pour améliorer les désordres métaboliques de l'obésité - - CAPTOR2017 - ANR-17-CE14-0009 - AAPG2017 - VALID, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Sorbonne Université (SU), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], Funding from the French National Agency of Research (ANR) is acknowledged and includes support from RHU collaborative grant CARMMA [15-RHUS-0003], from the Institute of Cardiometabolism and Nutrition (reference ANR-10-IAHU-05, to AL), ANR-14-CE12-0017-01 LIPOCAMD and ANR CAPTOR (ANR-17-CE14-0009). GM 615 and KC also received funds from AFERO, EFSD-Novo Nordisk, and SFD to support for salaries and consumables., ANR-10-IAHU-0005,ICAN,Institut de Cardiologie-Métabolisme-Nutrition(2010), ANR-14-CE12-0017,LIPOCAMD,LIPA, une nouvelle cible thérapeutique pour le traitement des maladies cardiométaboliques(2014), ANR-17-CE14-0009,CAPTOR,Contrôler la fonction des progéniteurs du tissu adipeux pour améliorer les désordres métaboliques de l'obésité(2017), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP]
Rok vydání: 2020
Předmět:
0301 basic medicine
collagen
MESH: Signal Transduction
Male
obesity
Receptor
Platelet-Derived Growth Factor alpha
[SDV.BA] Life Sciences [q-bio]/Animal biology
MESH: Bone Morphogenetic Proteins
MESH: Receptor
Platelet-Derived Growth Factor alpha
[SDV]Life Sciences [q-bio]
Adipose tissue
Muscle Proteins
Autophagy-Related Protein 7
Extracellular matrix
chloroquine
chemistry.chemical_compound
Adipose Tissue
Brown
Fibrosis
Transforming Growth Factor beta
Adipocyte
ScAT: subcutaneous adipose tissue
MESH: Animals
OvAT: ovarian adipose tissue
Promoter Regions
Genetic
Sex Characteristics
[SDV.BA]Life Sciences [q-bio]/Animal biology
Stem Cells
Cell biology
Extracellular Matrix
KO: knockout
Adipose Tissue
Adipogenesis
MESH: Fibrosis
Bone Morphogenetic Proteins
HFD: high-fat diet
Female
ATG7
MESH: Adipose Tissue
MESH: Sex Characteristics
Signal Transduction
Research Paper
subcutaneous adipose tissue
TGF-BMP: transforming growth factor-bone morphogenic protein ARTICLE HISTORY KEYWORDS ATG7
MESH: Trans-Activators
MESH: Stem Cells
Biology
MESH: Extracellular Matrix
Diet
High-Fat
ECM: extracellular matrix
MESH: Adipose Tissue
Brown
03 medical and health sciences
Paracrine signalling
MESH: Muscle Proteins
EpiAT: epididymal adipose tissue
MESH: Mice
Inbred C57BL
MESH: Promoter Regions
Genetic
medicine
Autophagy
MESH: Autophagy
Animals
Abbreviations: CQ: chloroquine
Heart Atria
Progenitor cell
Molecular Biology
MESH: Transforming Growth Factor beta
030102 biochemistry & molecular biology
GTF2IRD1: 25 general transcription factor II I repeat domain-containing 1
MESH: Autophagy-Related Protein 7
Cell Biology
medicine.disease
MESH: Male
Mice
Inbred C57BL
MESH: Diet
High-Fat
MicroRNAs
030104 developmental biology
chemistry
PDGFR: platelet derived growth factor receptor
Trans-Activators
MESH: Heart Atria
MESH: Female
MESH: MicroRNAs
Zdroj: Autophagy
Autophagy, 2020, 16 (12), pp.2156-2166. ⟨10.1080/15548627.2020.1717129⟩
Autophagy, 2020, 16 (12), Epub ahead of print. ⟨10.1080/15548627.2020.1717129⟩
Autophagy, Taylor & Francis, 2020, Epub ahead of print. ⟨10.1080/15548627.2020.1717129⟩
ISSN: 1554-8635
1554-8627
DOI: 10.1080/15548627.2020.1717129⟩
Popis: International audience; 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-CreErt2 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 Atg7lox/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.
Databáze: OpenAIRE
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