Cynandione A improves white adipose tissue homeostasis in high-fat diet-fed mice

OBJECTIVES: Cynandione A (CA), a major bioactive compound isolated from Cynanchum wilfordii Radix, is a crude drug traditionally used in East Asia. We have previously demonstrated that CA induces a beige adipocyte-like phenotype in vitro. This study aimed to investigate the in vivo effects of CA on white adipose tissue (WAT) function. METHODS: C57BL/6 J mice were fed a high-fat diet (HFD) and administered CA (5 or 15 mg/kg, intraperitoneally, once daily) for eight weeks. Body weight, glucose tolerance, insulin sensitivity, and serum parameters were evaluated. Histological analyses of WAT and liver were performed, and gene and protein expression related to beige adipocyte features and mitochondrial biogenesis were assessed in inguinal WAT (iWAT). KEY FINDINGS: CA treatment did not affect body weight, glucose tolerance, insulin sensitivity, or serum parameters. However, adipocyte size was significantly reduced in inguinal and epididymal WAT in mice treated with CA at 15 mg/kg (43.8% reduction, P < .001; 33.1% reduction, P = .021, respectively). Moreover, CA increased the expression of beige adipocyte-specific genes (Tmem26, 2.8-fold, P < .001; Cd137, 3.8-fold, P < .001) and mitochondrial marker proteins (UCP1, 2.1-fold, P = .007; TOM20, 2.2-fold, P < .001; VDAC, 1.6-fold, P = .019) in iWAT. CONCLUSIONS: CA modulates WAT plasticity and improves WAT homeostasis in HFD-fed mice.