Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed

Sánchez-Gurmaches, Joan; Guertin, David A.

doi:10.1038/ncomms5099

Cited by 316 publications

(335 citation statements)

References 28 publications

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“…Moreover, studies that observed adipogenic differentiation of MPs identified the myogenic progenitors by labelling for Pax7 or the myogenic regulatory factor Myf5. However, recent studies showed that Myf5 can be more widely distributed than previously appreciated and also labels white adipocytes 28. Moreover, a subpopulation of Myf5 + cells from extraocular muscle expresses Sca1 and is adipogenic 50.…”

Section: Discussionmentioning

confidence: 98%

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Gorski

Mathes

Krützfeldt

2018

J cachexia sarcopenia muscle

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BackgroundIntramuscular fatty infiltration is generally associated with the accumulation of white adipocytes in skeletal muscle and unfavourable metabolic outcomes. It is, however, still unclear whether intramuscular adipocytes could also acquire a brown‐like phenotype. Here, we detected intramuscular expression of brown adipocyte markers during fatty infiltration in an obesity‐resistant mouse strain and extensively compared the potential of two different stem cell populations residing in skeletal muscle to differentiate into brown‐like adipocytes.MethodsFatty infiltration was induced using intramuscular glycerol or cardiotoxin injection in the tibialis anterior muscles of young or aged 129S6/SvEvTac (Sv/129) mice or interleukin‐6 (IL‐6) knockout mice, and the expression of general and brown adipocyte markers was assessed after 4 weeks. Fibro/adipogenic progenitors (FAPs) and myogenic progenitors were prospectively isolated using fluorescence‐activated cell sorting from skeletal muscle of male and female C57Bl6/6J and Sv/129 mice, and monoclonal and polyclonal cultures were treated with brown adipogenic medium. Additionally, FAPs were differentiated with medium supplemented or not with triiodothyronine.ResultsAlthough skeletal muscle expression of uncoupling protein 1 (Ucp1) was barely detectable in uninjected tibialis anterior muscle, it was drastically induced following intramuscular adipogenesis in Sv/129 mice and further increased in response to beta 3‐adrenergic stimulation. Intramuscular Ucp1 expression did not depend on IL‐6 and was preserved in aged skeletal muscle. Myogenic progenitors did not form adipocytes neither in polyclonal nor monoclonal cultures. Fibro/adipogenic progenitors, on the other hand, readily differentiated into brown‐like, UCP1+ adipocytes. Uncoupling protein 1 expression in differentiated FAPs was regulated by genetic background, sex, and triiodothyronine treatment independently of adipogenic differentiation levels.ConclusionsIntramuscular adipogenesis is associated with increased Ucp1 expression in skeletal muscle from obesity‐resistant mice. Fibro/adipogenic progenitors provide a likely source for intramuscular adipocytes expressing UCP1 under control of both genetic and hormonal factors. Therefore, FAPs constitute a possible target for therapies aiming at the browning of intramuscular adipose tissue and the metabolic improvement of skeletal muscle affected by fatty infiltration.

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Section: Discussionmentioning

confidence: 98%

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Gorski

Mathes

Krützfeldt

2018

J cachexia sarcopenia muscle

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“…Although an endothelial origin for adipocytes could contradict the work of Seale and colleagues and Sanchez-Gurmaches and colleagues, describing adipocytes arising from Myf5 + myogenic precursors (Sanchez-Gurmaches and Guertin, 2014b;Seale et al, 2008;Tran et al, 2012), De Angelis and colleagues reported the existence of progenitor cells from embryonic dorsal aorta, expressing both endothelial (including VE-cadherin) and myogenic markers (i.e. Myf5) (De Angelis et al, 1999).…”

Section: Endothelial Cellsmentioning

confidence: 94%

Heterogeneity of adipose tissue in development and metabolic function

Schoettl

Fischer

Ussar

2018

Journal of Experimental Biology

175

139

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Adipose tissue is a central metabolic organ. Unlike other organs, adipose tissue is compartmentalized into individual depots and distributed throughout the body. These different adipose depots show major functional differences and risk associations for developing metabolic syndrome. Recent advances in lineage tracing demonstrate that individual adipose depots are composed of adipocytes that are derived from distinct precursor populations, giving rise to different populations of energy-storing white adipocytes. Moreover, distinct lineages of energy-dissipating brown and beige adipocytes exist in discrete depots or within white adipose tissue depots. In this Review, we discuss developmental and functional heterogeneity, as well as sexual dimorphism, between and within individual adipose tissue depots. We highlight current data relating to the differences between subcutaneous and visceral white adipose tissue in the development of metabolic dysfunction, with special emphasis on adipose tissue expansion and remodeling of the extracellular matrix. Moreover, we provide a detailed overview of adipose tissue development as well as the consensus and controversies relating to adult adipocyte precursor populations.

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“…It is well established that Myf5-Cre targets cells that give rise to skeletal muscle and interscapular BAT (iBAT) (Seale et al, 2008). Myf5-Cre also targets interscapular WAT (iWAT) and retroperitoneal WAT (rWAT) but not inguinal WAT (ingWAT) or perigonadal WAT ( pWAT) (Sanchez-Gurmaches and Guertin, 2014;Sanchez-Gurmaches et al, 2012). Myf5-Cre;PDGFRα +/D842V mutants (hereafter referred to as Myf5-D842V) were viable, although an overall smaller body size became apparent around postnatal day (P)5.…”

Section: Pdgfrαmentioning

confidence: 99%

PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis

2017

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Adipose tissue is distributed in depots throughout the body with specialized roles in energy storage and thermogenesis. PDGFRα is a marker of adipocyte precursors, and increased PDGFRα activity causes adipose tissue fibrosis in adult mice. However, the function of PDGFRα during adipose tissue organogenesis is unknown. Here, by analyzing mice with juxtamembrane or kinase domain point mutations that increase PDGFRα activity (V561D or D842V), we found that PDGFRα activation inhibits embryonic white adipose tissue organogenesis in a tissue-autonomous manner. By lineage tracing analysis, we also found that collagen-expressing precursor fibroblasts differentiate into white adipocytes in the embryo. PDGFRα inhibited the formation of adipocytes from these precursors while favoring the formation of stromal fibroblasts. This imbalance between adipocytes and stromal cells was accompanied by overexpression of the cell fate regulator Zfp521. PDGFRα activation also inhibited the formation of juvenile beige adipocytes in the inguinal fat pad. Our data highlight the importance of balancing stromal versus adipogenic cell expansion during white adipose tissue development, with PDGFRα activity coordinating this crucial process in the embryo.

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Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed

Cited by 316 publications

References 28 publications

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

Heterogeneity of adipose tissue in development and metabolic function

PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis

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