Tectorigenin regulates adipogenic differentiation and adipocytokines secretion via PPARγ and IKK/NF-κB signaling

Abstract

Context: Obesity is associated with a number of diseases with metabolic abnormalities such as type 2 diabetes (T2D). Objective: We investigate the effects of tectorigenin on 3T3-L1 preadipocyte differentiation and adipocytokines secretion. Materials and methods: The effects of tectorigenin on adipocyte differentiation were studied using Oil Red O staining. Effects of tectorigenin on adipogenesis-related genes expression and adipocytokines secretion were measured by the real-time quantitative RT-PCR and ELISA method, respectively. Reporter gene assays were performed to determine the PPARγ and NF-κB transactivation. We also used [3H]-2-deoxy-D-glucose to study the glucose uptake, and the IKK/ NF-κB signaling pathway was assessed by western blot analysis. HFD/STZ rats were used to evaluate the therapeutic efficacies of tectorigenin. Results: Tectorigenin 10, 25, 50, and 75 μM inhibited 3T3-L1 adipogenesis and related genes transcription. TNF-α-induced changes of IL-6, MCP-1, as well as adiponectin in 3T3-L1 were markedly reversed by tectorigenin at 75 μM. Further investigation using reporter gene revealed that tectorigenin was a partial PPARγ agonist with an IC50 value of 13.3 μM. Tectorigenin improved basal and insulin-stimulated glucose uptake in mature 3T3-L1 adipocytes. Moreover, tectorigenin antagonized TNF-α-induced NF-κB transactivation and p65 nuclear translocation. Although tectorigenin (50 and 100 mg/kg) displayed the ability to promote insulin sensitivity and improve glucose metabolism in HFD/STZ rats, it did not cause significant side effects such as body weight gain, fluid retention, or cardiac hypertrophy. Discussion and conclusion: These results suggest that tectorigenin may ameliorate hyperglycemia by blocking preadipocyte differentiation and adipocytokines secretion in which PPARγ and NF-κB signaling pathways were involved.