Fibrosis in epidydimal white adipose tissue develops with chronic high fat diet feeding, which has been associated with decreased energy expenditure, insulin resistance and increased inflammation etc. Beige/brite adipocytes in typical white adipose tissue depots, have therapeutic potential of improving metabolism through increasing energy consumption. We previously showed that Mice with deletion of Smad3 or TGFβ receptor 1 (TβRI) kinase exhibit metabolic benefits associated with beige adipogenesis. In the current study, we investigated the relationship between high fat diet-induced fibrosis and beige adipogenesis.


We compared the beige differentiation capacity of stromal vascular fraction (SVF) from normal chow fed mice (NC) and high fat diet-fed (HFD) mice. To investigated TGFβ signaling pathway role in this process we used adipose tissue specific deletion of TβRI.


We found that Itga5+ positive fibrotic progenitor increases with HFD feeding, concomitant with decreased beige differentiation capacity in the SVF of eWAT. At the progenitor stage, TGFβ treatment dramatically increased Itga5+ fibrotic progenitors, decreasing PDGFRα adipogenic progenitors. Consistently, TGFβ suppressed whereas inhibition of TβRI with SB431542 enhanced brown/beige gene expression and proton leak-driven OCR induced by chronic treatment with the PPARγ agonist rosiglitazone or acute stimulation with the β3-adrenergic receptor agonist, CL316,243. Knockout of TβRI decreased Itga5+ fibrotic progenitors population in SVF and inhibited fibrosis in eWAT of HFD fed mice.


We unraveled an intrinsic negative correlation between HFD-induced fibrotic progenitor population and beige adipogenesis capacity. TGFβ upregulated in HFD negatively regulates of beige adipogenesis through increasing population of fibrotic progenitors. Blocking TGFβ signaling pathway could substantially increase beige mediated energy consumption while supressing fibrosis in white adipose tissue