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

• Published in: Cell reports (Cambridge) 2019-04, Vol.27 (2), p.323-333.e5
• Main Authors: Girousse, Amandine, Gil-Ortega, Marta, Bourlier, Virginie, Bergeaud, Célia, Sastourné-Arrey, Quentin, Moro, Cédric, Barreau, Corinne, Guissard, Christophe, Vion, Julie, Arnaud, Emmanuelle, Pradère, Jean-Philippe, Juin, Noémie, Casteilla, Louis, Sengenès, Coralie
• Format: Article
• Language: English
• Subjects: adipose stem or stromal cells; AMD3100; chemotaxis; CXCR4/CXCL12; ectopic adipocytes; Human health and pathology; intramuscular adipocyte; Life Sciences; lymphatic system; thiazolidinedione; Tissues and Organs; type 2 diabetes
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.03.038

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. [Display omitted] •ASCs egress subcutaneous adipose tissue during dietary challenge•ASCs infiltrate muscle and differentiate into adipocytes, disturbing metabolism•Dietary-driven ASC trafficking relies on CXCL12 signals•Pioglitazone can prevent dietary-driven ASC infiltration in muscle Girousse et al. show that, in mice fed a high-fat diet, adipose stromal cells (ASCs) can egress subcutaneous adipose tissue and infiltrate skeletal muscle to form ectopic adipocytes, causing metabolic disturbance. ASC trafficking is regulated by the CXCR4/CXCL12 axis, and pioglitazone intermittent treatment can prevent muscle ectopic lipid deposition.