Abstract Body: Adipose tissue performs diverse functions, including energy storage, metabolic regulation, and endocrine signaling. In obesity, which affects over 40% of U.S. adults, adipose tissue becomes dysfunctional, exhibiting increased inflammation, fibrosis, and insulin resistance. Proper extracellular matrix (ECM) formation is essential for healthy adipose tissue expansion. Periostin (Postn), a secreted matricellular protein involved in ECM remodeling and tissue fibrosis, has been suggested to influence adipose tissue homeostasis. However, its functional role remains unexplored. This study aims to investigate how Postn regulates white adipose tissue (WAT) remodeling and metabolism.
In our Postn global knockout mice (Postn^MCM/MCM), we found the adult knockout mice exhibited reduced body weight and smaller white fat pads, including subcutaneous and visceral fat, while brown fat remained unaffected. Additionally, the subcutaneous WAT (sWAT) from these mice displayed elevated inflammatory and fibrosis markers, suggesting that Postn deficiency may drive adipose dysfunction. Interestingly, markers of WAT beiging were increased, indicating a potential metabolic shift. By utilizing our Postn lineage tracing model (Postn^MCM/+-tdTomato), Postn^lin cells were identified in both sWAT sections and stromal vascular fraction (SVF) derived primary cultures. These progenitors exhibited a capacity to undergo adipogenesis and differentiate into mature adipocytes in vitro. Analysis of RNA-sequencing data from Emont et al. revealed an adipose progenitor cluster with high Postn expression, which exhibited greater differentiation potential. Validating these findings in our SVF primary cultures, we observed that both Postn expression and secretion peaked at day 2 of adipogenic differentiation, precisely as preadipocytes transition toward mature adipocytes. Consistently, pseudo-time trajectory analysis showed that this Postn-expressing progenitor cluster appeared as the terminal cluster among six identified clusters during adipocyte development.
In conclusion, we found loss of Postn blunts healthy WAT expansion and alters metabolic status, highlighting a critical role for Postn in adipose tissue remodeling. These effects may be mediated through the regulation of adipogenesis, as Postn-expressing progenitor cells exhibit greater differentiation potential.