Abstract
Gestational diabetes mellitus (GDM) is associated with increased inflammation in adipose tissues. Fibroblast growth factor 21 (FGF21) is an endocrine hormone which signals to multiple tissues to regulate metabolism. However, its role in GDM remains largely unknown. In this study, we found that impaired FGF21 signaling in GDM correlates with worsened inflammation and insulin resistance in white adipose tissues in mice. Mechanistically, the pregnancy-related upregulation of FGF21 signaling in adipocytes promotes the differentiation of regulatory T cells (Tregs), which are critical for reducing pregnancy-induced adipose tissue inflammation. The anti-inflammatory effects of FGF21 may involve linolenic acid-mediated PGE2 synthesis in adipocytes. These findings underscore FGF21's role in mediating crosstalk between mature adipocytes and immune cells in white adipose tissue and suggest that targeting FGF21 signaling and its downstream metabolites could offer a potential therapeutic approach for GDM in humans.