Dendrobium Officinale Polysaccharide Attenuates Insulin Resistance and Abnormal Lipid Metabolism in Obese Mice

Abstract

Objectives: Dendrobium officinale polysaccharide (DOP), a traditional Chinese medicine, has several pharmacological actions in hepatoprotection, cancer chemotherapy, hypoglycemia, anti-fatigue effect, and gastric ulcer protection, among others. However, the effect of DOP in obesity-associated insulin resistance and lipid metabolism remains unknown. This study aimed to investigate the role of DOP in insulin resistance and abnormal lipid metabolism in obese mice. Materials and Methods: The insulin resistance models were established using 3T3-L1 adipocytes, C2C12 myocytes, and primary cultured hepatocytes incubated in palmitate acid. After treatment with DOP, insulin-stimulated glucose uptake of 3T3-L1 adipocytes and C2C12 myocytes and glucose output of primary cultured hepatocytes were detected. In addition, the insulin-stimulated phosphorylation of AKT was confirmed by western blot. Related mechanism studies were confirmed by qRT-PCR and western blotting. DOP was orally administrated in obese mice. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), and insulin tolerance test (ITT) were measured to evaluate insulin sensitivity of mice. Lipid analysis was conducted to evaluate the effect of DOP on lipid metabolism in obese mice. Results: In vitro, DOP treatment ameliorated palmitic acid-induced insulin resistance in adipocytes, myocytes, and hepatocytes. Mechanistically, DOP regulated cellular insulin sensitivity via peroxisome proliferator-activated receptor-γ (PPAR-γ). Furthermore,administration of DOP significantly reduced the insulin resistance of obese mice, as seen by decreased levels of fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). In addition, DOP treatment attenuated high fat diet(HFD)-induced liver lipid accumulation by reducing liver triglycerides (TG), plasma free fatty acid (FFA), serum cholesterol (TC), TG, and low-density lipoprotein cholesterol (LDL-C) levels, and increasing HDL-C levels. Conclusions: DOP could improve obesity-associated insulin resistance and abnormal lipid metabolism by acting on PPAR-γ, which may serve as a potential therapeutic agent for obesity-associated insulin resistance and lipid metabolism disorder. Funding Statement: This work was supported by the Natural Science Foundation of Hunan Province (2020JJ4799). Declaration of Interests: There are no potential conflicts of interest to declare. Ethics Approval Statement: All protocols of animal care and experiment were reviewed and approved by the Institutional Animal Care and Use Committee of the Laboratory Animal Research Center at Xiangya Medical School of Central South University, China.