TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway

Abstract

Fat metabolism: protecting against obesity-related metabolic disordersStudying a protein called TGFBI, which regulates adipose expansion, may help the development of new approaches to protect against obesity and related metabolic disorders such as type II diabetes. White adipose tissue (body fat) stores energy, and brown adipose tissue generates heat. Promoting "browning" of adipose tissue may help protect against obesity. Proteins that influence adipose microenvironment can be involved in metabolic diseases, so Seul Gi Lee and Ju-Ock Nam at Kyungpook National University, Taeg Kyu Kwon at Keimyung University, both in Daegu, South Korea, and co-workers investigated how TGFBI affects adipose metabolism in a mouse model. Deleting TGFBI in mice promoted the transformation of white adipose tissue to brown, protecting mice against weight gain and increase in adipose tissue. These results offer insights into potential therapies for obesity and related disorders via TGFBI regulation. Extracellular matrix proteins are associated with metabolically healthy adipose tissue and regulate inflammation, fibrosis, angiogenesis, and subsequent metabolic deterioration. In this study, we demonstrated that transforming growth factor-beta (TGFBI), an extracellular matrix (ECM) component, plays an important role in adipose metabolism and browning during high-fat diet-induced obesity. TGFBI KO mice were resistant to adipose tissue hypertrophy, liver steatosis, and insulin resistance. Furthermore, adipose tissue from TGFBI KO mice contained a large population of CD11b(+) and CD206(+) M2 macrophages, which possibly control adipokine secretion through paracrine mechanisms. Mechanistically, we showed that inhibiting TGFBI-stimulated release of adipsin by Notch-1-dependent signaling resulted in adipocyte browning. TGFBI was physiologically bound to Notch-1 and stimulated its activation in adipocytes. Our findings revealed a novel protective effect of TGFBI deficiency in obesity that is realized via the activation of the Notch-1 signaling pathway.