Abstract

Obesity is associated with an increased risk of insulin resistance in which activation and accumulation of adipose tissue macrophages (ATMs) are suggested to be responsible for the pathological change. We found that selenocysteine insertion sequence-binding protein 2 (SBP2) plays a role in monitoring insulin sensitivity in obesity. Suppression of SBP2 in ATMs from obese mice is associated with adipose tissue inflammation by which ATMs initiate metabolic activation, with increased intracellular reactive oxygen species and inflammasome leading to IL-1β-associated proliferation and infiltration and resulted in increased accumulation of fat tissue, while fasting blood glucose level and glucose tolerance are elevated. Tang-ning-tong-luo (TNTL) is a traditional herbal medicine formula inherited from the Hmong (Miao). We found that TNTL can improve insulin sensitivity in experimental models by inducing SBP2 expression in adipose tissue macrophages. In an open-label clinical study, TNTL was shown to exhibit significant improvement in hyperglycemia in diabetic patients. Our study suggested that TNTL is a potential drug for SBP2 regulation, which is improving obesity-induced insulin resistance in both pre-clinical and clinical studies.