Sijunzi decoction improves lipid metabolism via regulation of Wnt/β-catenin signaling pathway in diabetic mice and 3T3-L1 cells

Abstract

Ethnopharmacological relevance

Sijunzi decoction (SJZD), a traditional Chinese medicinal formula with the functions of invigorating the Spleen and replenishing Qi, has been clinically used for the management of diabetes, but its actions and underlying mechanisms on diabetic lipid metabolism remain largely unknown.

Aim of the study

To explore the effects of SJZD on lipid metabolism disorders and its association with the Wnt/β-catenin pathway in the white adipose tissue of diabetic mice and 3T3-L1 cells.

Materials and methods

The diabetic lipid metabolism disorders models were established by high-fat diet/streptozotocin in mice and palmitic acid in 3T3-L1 cells, respectively. The effects of SJZD on total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and glucose consumption were determined by biochemical assay. Hematoxylin-eosin (H&E) staining was used to examine pathological alterations in adipose tissues. Oil red O staining was used to evaluate the differentiation of lipid droplets in 3T3-L1 adipocytes. The expression levels of Wnt10b, β-catenin, CCAAT enhancer binding protein α (C/EBP-α), sterol regulatory element-binding protein 1 (SREBP-1c), acetyl-CoA carboxylase-1 (ACC1), peroxisome proliferator-activated receptor γ (PPAR-γ), fatty acid synthase (FASN), adipose triglyceride lipase (ATGL) were examined by Western blot and/or qRT-PCR. In addition, the main components of SJZD and SJZD-containing serum (SCS) were identified by UPLC-Q-TOF-MS/MS.

Results

SJZD reduces the body fat ratio, fasting blood glucose levels, adipose tissue index and serum levels of TC, TG, and LDL, and increases the body weight, lean ratio, and serum HDL levels, as well as prevents the adipocytes hypertrophy in diabetic mice. In addition, SJZD, SCS and its ingredients (Ginsenoside Rb1 and Glycyrrhetinic acid) inhibit lipid synthesis, TG levels and promote glucose consumption in diabetic mice and 3T3-L1 adipocytes. These interventions decrease the expressions of PPAR-γ, SREBP-1c, C/EBP-α, FASN, ACC1 and P-β-catenin, and increase the expressions of ATGL, Wnt10b and β-catenin.

Conclusion

SJZD regulates the Wnt/β-catenin signaling pathway to preserve lipid metabolism homeostasis in diabetes. GRb and Gac may constitute the material basis of SJZD in attenuation of diabetic lipid metabolism disorders. These findings highlight a novel strategy for the treatment of diabetes.