Yunpi Heluo decoction reduces ectopic deposition of lipids by regulating the SIRT1-FoxO1 autophagy pathway in diabetic rats.

Context: Yunpi Heluo (YPHL) decoction is a Chinese herbal formula with particular advantages for treating type 2 diabetes. Yet, its exact mechanism of action is not fully understood. Objective: To examine the therapeutic effect of YPHL on ectopic lipid deposition (EDL) in Zucker diabetic fatty (ZDF) rats and the underlying mechanism. Materials and methods: The ZDF Rats were randomized into five groups, including model, YPHL (200mg/kg/d for 10 weeks), SIRT1-overexpression (injected with HBAAV2/9-r-SIRT1-30-flag-GFP), NC (injected with HBAAV2/9-CMV-GFP as blank control) and control group. Pancreatic b-cells obtained from high-lipid-high-glucose fed rats were treated with YPHL (10mg/mL) for 48 h. Lipid deposition and autophagosomes were analyzed by transmission electron microscopy. Intracellular H₂O₂ and ROS concentrations were measured by flow cytometry. SIRT1, FOXO1, LC3 and P62 mRNA and protein levels were analyzed using qRT-PCR and Western blots. Results: Compared with the model group, blood glucose levels in YPHL and si-SIRT1 groups were reduced by 19.3% and 27.9%, respectively. In high-lipid-high-glucose cells treated with YPHL, lipid droplets were reduced and decrease in apoptosis rate (38.6%), H₂O₂ (31.2%) and ROS (44.5%) levels were observed. After YPHL intervention or SIRT1 overexpression, LC3 and p62 expression increased. Protein expression of SIRT1 and LC3 in model, si-SIRT1, si-NC and si-SIRT1þYPHL groups was lower than those in control group, while FoxO1 expression was increased. All of these protein level alterations were reversed in the si-NCþYPHL group. Discussion and conclusions: YPHL reduced EDL by regulating the SIRT1-FoxO1 autophagy pathway in diabetic rats, which could lead to future perspectives for the treatment of diabetes. [ABSTRACT FROM AUTHOR]