Distinct adipocyte progenitor cells are associated with regional phenotypes of perivascular aortic fat in mice

Perivascular adipose tissue depots around the aorta are regionally distinct and have specific functional properties. Thoracic aorta perivascular adipose tissue (tPVAT) expresses higher levels of thermogenic genes and lower levels of inflammatory genes than abdominal aorta perivascular adipose tissue (aPVAT). It is not known whether this distinction is due to the in-vivo functional environment or to cell-autonomous traits that persist outside the in-vivo setting. In this study, we asked whether the progenitor cells in tPVAT and aPVAT have cell-autonomous traits that lead to formation of regionally distinct PVAT.

We performed microarray analysis of thoracic and abdominal peri-aortic adipose tissues of C57Bl/6J mice to define gene expression profile of each depot. To derive adipocyte progenitor cells, C57Bl/6J mice were sacrificed and thoracic and abdominal aorta fragments were embedded in Matrigel and cultured under pro-angiogenic conditions. Adipogenesis was induced using the Ppar-γ agonist rosiglitazone, a thiazolidinedione (TZD). TZD-induced adipocyte populations were analyzed using immunofluorescence and qRT-PCR.

Microarray analysis showed that tPVAT expressed higher levels of transcription factors related brown adipose tissue development compared to aPVAT. Classic brown adipose tissue (BAT) genes such as Ucp-1, Prdm16, Dio2, Slc27a displayed a concordant trend of higher level expression in tPVAT, while white adipose tissue (WAT) genes such as Hoxc8, Nnat, Sncg, and Mest were expressed at a higher level in aPVAT. The adipokines resistin and retinol binding protein 4 were also higher in aPVAT. Furthermore, adipocyte progenitors from abdominal and thoracic aortic rings responded to TZD with expression of canonical adipocyte genes Acrp30, Plin1, and Glut4. Adipocytes differentiated from thoracic aorta progenitors displayed markedly higher induction of Ucp-1 and Cidea.

Thoracic aorta PVAT expresses higher levels of brown adipocyte transcription factors than aPVAT. Precursor cells from the thoracic aorta give rise to adipocytes that express significantly higher levels of Ucp-1 and Cidea ex vivo, suggesting that progenitor cells in tPVAT and aPVAT have cell-autonomous properties that dictate adipocyte phenotype.