Fibrosis is a pathological state caused by excess deposition of
extracellular matrix proteins in a tissue. Male
bovine growth hormone (bGH) transgenic mice experience metabolic dysfunction with a marked decrease in lifespan and with increased
fibrosis in several tissues including white adipose tissue (WAT), which is more pronounced in the subcutaneous (Sc) depot. The current study expanded on these initial findings to evaluate WAT
fibrosis in female bGH mice and the role of
transforming growth factor (TGF)-β in the development of WAT
fibrosis. Our findings established that female bGH mice, like males, experience a depot-dependent increase in WAT
fibrosis, and bGH mice of both sexes have elevated circulating levels of several markers of
collagen turnover. Using various methods, TGF-β signaling was found unchanged or decreased-as opposed to an expected increase-despite the marked
fibrosis in WAT of bGH mice. However, acute GH treatments in vivo, in vitro, or ex vivo did elicit a modest increase in TGF-β signaling in some experimental systems. Finally, single nucleus
RNA sequencing confirmed no perturbation in TGF-β or its receptor gene expression in any WAT cell subpopulations of Sc bGH WAT; however, a striking increase in B lymphocyte infiltration in bGH WAT was observed. Overall, these data suggest that bGH WAT
fibrosis is independent of the action of TGF-β and reveals an intriguing shift in immune cells in bGH WAT that should be further explored considering the increasing importance of B cell-mediated WAT
fibrosis and pathology.