The Release of Adipose Stromal Cells from Subcutaneous Adipose Tissue Regulates Ectopic Intramuscular Adipocyte Deposition

Amandine Girousse (1) , Marta Gil-Ortega (1) , Virginie Bourlier (2) , Célia B Bergeaud (3, 1) , Quentin Sastourné-Arrey (1) , Cédric Moro (4) , Corinne Barreau (1) , Christophe Guissard (1) , Julie Vion , Emmanuelle Arnaud (5, 1) , Jean-Philippe Pradère (6) , Noémie Juin (1) , Louis Casteilla (5, 1) , Coralie Sengenes (1)

1 STROMALab
2 I2MR - Institut de médecine moléculaire de Rangueil
3 UBC - University of British Columbia
4 Service Pharmacologie Clinique [CHU Toulouse]
5 NPTME - Neurobiologie, plasticité tissulaire et métabolisme énergétique
6 Unité de recherche sur les obésités

Ectopic lipid deposition (ELD) is defined by excess fat storage in locations not classically associated with adipose tissue (AT) storage. ELD is positively correlated with insulin resistance and increased risk of metabolic disorders. ELD appears as lipid droplets or adipocytes, whose cell origin is unknown. We previously showed that subcutaneous AT (ScAT) releases adipocyte progenitors into the circulation. Here, we demonstrate that triggering or preventing the release of adipocyte precursors from ScAT directly promoted or limited ectopic adipocyte formation in skeletal muscle in mice. Importantly, obesity-associated metabolic disorders could be mimicked by causing adipocyte precursor release without a high-fat diet. Finally, during nutrient overload, adipocyte progenitors exited ScAT, where their retention signals (CXCR4/CXCL12 axis) were greatly decreased, and further infiltrated skeletal muscles. These data provide insights into the formation of ELD associated with calorie overload and highlight adipocyte progenitor trafficking as a potential target in the treatment of metabolic diseases..

Domaines: Physiologie [q-bio.TO]

Amandine Girousse, Marta Gil-Ortega, Virginie Bourlier, Célia B Bergeaud, Quentin Sastourné-Arrey, et al.. The Release of Adipose Stromal Cells from Subcutaneous Adipose Tissue Regulates Ectopic Intramuscular Adipocyte Deposition. Cell Reports, 2019, 27 (2), pp.323-333.e5. ⟨10.1016/j.celrep.2019.03.038⟩. ⟨hal-02136523⟩