Marrow adipose tissue (MAT) was identified in the bone marrow (BM) more than a century ago and until very recently was thought to be nothing more than filler. Although recent data suggests that MAT has characteristics of brown adipose tissue (BAT) or beige adipocytes, little is known about the origin, development, and function of MAT because the BM adipocyte precursor/progenitor cell remains unknown. 

We have performed lineage tracing of BM adipocytes following induction of BM adipogenesis with either rosiglitazone-enriched (rosi) diet or irradiation of double fluorescent mT/mG reporter mice (which harbor a floxed membrane targeted tdTomato cassette (mT) upstream of a Cre-responsive membrane targeted eGFP cassette (mG)) to determine the ontogeny of BM adipocytes and identity of BM adipocyte progenitor cells. Following either irradiation or rosi diet, all BM adipocytes were eGFP+ and therefore traced by expression of Cre-recombinase in Adiponectin-Cre:mT/mG and Osx1-Cre:mT/mG mice. In contrast, adipocytes were not traced (tdTomato+) in Vav1-Cre:mT/mG or Myf5-Cre:mT/mG mice. 

B6 mice fed a methionine restricted (MR) diet show a pronounced induction of multilocular beige adipocytes in their inguinal depot (IWAT) and a concomitant increase in MAT as compared to mice on control diet. However, unlike the IWAT, none of the marrow adipocytes were multilocular. Using immunohistochemistry, IWAT from the MR mice stained with anti-UCP-1 confirmed the presence of beige adipocytes. In contrast, MAT from those same mice was uniformly UCP-negative. 

We previously demonstrated that all adipocytes in classical white adipose tissue (WAT) depots were traced in PdgfRα-Cre:mT/mG mice due to expression of PdgfRα in WAT precursor cells. In contrast, between 50-70% of BM adipocytes were eGFP+ in the same mice. To better understand the relationship between MAT and WAT we examined PdgfRa-cre:insulinRfl/fl mice. These mice were found to have a marked increase in MAT and a paucity of WAT, suggesting that the requirement of insulin signaling for adipocyte formation is another distinguisher between MAT and WAT. 

Mouse tibias and femora can be made deficient in MAT from birth using a genetic approach. These bones have increased bone mineral density and are biomechanically stronger. 

Together, the uniform tracing of BM adipocytes by the endosteal cell/osteoblast promoter Osx1, the lack of tracing of BM adipocytes by Myf5 (which traces all brown adipocytes), the absence of multilocular, UCP-1 positive marrow adipocytes, and the formation of MAT in the absence of insulin receptor indicate that the MAT depot is distinct from BAT, WAT, or beige fat. MAT is not “just filler” but has demonstrable functions.

Invited by Xavier Houard.

 

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Centre De Rercherche (CdR) Saint-Antoine
INSERM - UMR S 938

Hôpital St-Antoine

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Centre De Recherche Saint-Antoine

Le CRSA, UMRS_938 a été renouvelé par l'Inserm et l'UPMC pour 5 ans (Janvier 2014-Décembre 2018).

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Présentation du centre

Le CRSA regroupe un très fort potentiel pour la recherche biomédicale à la fois fondamentale et translationnelle. Les travaux de recherche sont réalisés en collaboration avec les services cliniques et biologiques des hôpitaux Saint-Antoine-Tenon-Armand Trousseau appartenant au même groupe hospitalier. Le CRSA est composé de 14 équipes de recherche labelisées par l'Inserm et l'UPMC et une équipe administrative, localisées principalement sur le site de l'hôpital Saint-Antoine et de l'hôpital Armand Trousseau.

Activités scientifiques

Le CRSA a deux thématiques scientifiques étroitement liées : la recherche en cancérologie et hématologie; et la recherche sur le métabolisme et l'inflammation. Ces thématiques sont étudiées au niveau fondamental, physiopathologique, préclinique et clinique.

Équipements collectifs et plateformes techniques

Le CRSA dispose de plateformes techniques (Plateformes d'hébergement et d'expérimentation animale, laboratoires L2, L3 ) mais a également accès sur le site au réseau des plateformes UPMC telles que la spectrométrie de masse, lipidomique et protéomique, l'imagerie et la cytométrie en flux.