Role of transforming growth factor-β1 in regulating adipocyte progenitors

Abstract

Adipose tissue (AT) metabolism involves coordinating various cells and cellular processes to regulate energy storage, release, and overall metabolic homeostasis. Therein, macrophage and its cytokine are important in controlling tissue homeostasis. Among cytokines, the role of transforming growth factor-β1 (Tgf-β1), a cytokine abundantly expressed in CD206⁺ M2 macrophage and correlated with the expansion of AT and fibrosis, in AT metabolism remains unknown. We used CD206CreER^T2; Tgf-β1^f/f mouse model in which the Tgf-β1 gene was conditionally deleted in CD206⁺ M2 macrophages followed by tamoxifen administration, to investigate the role of the Tgf-β1 gene in glucose and insulin metabolism. Our data demonstrated that lack of CD206⁺ M2 macrophages derived Tgf-β1 gene improved glucose metabolism and insulin sensitivity by enhancing adipogenesis via hyperplasia expansion. The Tgf-β1 gene, specifically from CD206⁺ M2 macrophages, deletion stimulated APs’ proliferation and differentiation, leading to the generation of smaller mature adipocytes, therefore maintaining insulin sensitivity and improving glucose metabolism under normal chow conditions. Our study brings a new perspective that Tgf-β1 gene deletion specific from CD206⁺ M2 macrophage promotes adipocyte hyperplasia, improving glucose homeostasis. Thus, deletion of the Tgf-β1 gene derived from CD206⁺ M2 macrophage might be a potential strategy for preventing obesity and type 2 diabetes.