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

Jian Qu,Xinyan Xie,Hang Li,Xiaobo Liao,Qiong Lu,Song Huang,Shengyu Tan,Zhi-Ang Zhou,Wenqiang Wu,Haihong Zhu,Jiaojiao Wang

doi:10.3389/fphar.2021.659626

Abstract

Objectives: Dendrobium officinale polysaccharide (DOP) is the main active ingredient in a valuable traditional Chinese medicine, which exerts several pharmacological activities including hepatoprotection and hypoglycemic effects. However, the effects of DOP on obesity-associated insulin resistance (IR) and lipid metabolism remain unknown. This study aimed to investigate the role of DOP in IR and abnormal lipid metabolism in obese mice. Methods: IR models were established using 3T3-L1 adipocytes, C2C12 myocytes, and primary cultured hepatocytes exposed to palmitate acid. After treatment with DOP, insulin-stimulated glucose uptake, glucose release, and AKT phosphorylation was detected. Fasting blood glucose, fasting serum insulin, the glucose tolerance test (GTT), and the insulin tolerance test (ITT) were measured to evaluate IR of obese mice. Lipid analysis was conducted to evaluate the effects of DOP on lipid metabolism in obese mice. Results: In vitro, DOP treatment ameliorated palmitic acid-induced IR in adipocytes, myocytes, and hepatocytes. DOP regulated cellular insulin sensitivity via the peroxisome proliferator-activated receptor-γ (PPAR-γ). Furthermore, administration of DOP significantly reduced the IR and visceral adipose tissue (VAT) inflammation of diet-induced obese (DIO) and the genetically-induced obesity mice (ob/ob) mouse models. In addition, DOP treatment attenuated the high-fat diet (HFD)-induced liver lipid accumulation by reducing liver triglycerides (TG), plasma free fatty acid (FFA), serum cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing HDL-C levels. Conclusion: DOP could improve obesity-associated IR and abnormal lipid metabolism through its activities on PPAR-γ, and may serve as a potential therapeutic agent for obesity-associated insulin resistance and lipid metabolism disorder.

Highlights

With rapid economic growth, obesity is becoming an increasing health concern worldwide
Ob/ob mice harbor a recessive mutation in leptin and are characterized by hyperphagia, obesity, hyperinsulinemia, insulin-resistance (IR), and hyperglycemia; they are commonly used as a model for studies of diabetes and obesity
To explore whether Dendrobium officinale polysaccharide (DOP) participated in the regulation of insulin sensitivity, we treated palmitate acid (PA)-induced adipocytes, myocytes, and hepatocytes with DOP

Summary

Introduction

Obesity is becoming an increasing health concern worldwide. IR refers to the reduction of insulin sensitivity and response to insulin target organs and tissues (liver, adipose tissue, skeletal muscle) due to varied reasons (Samuel and Shulman, 2012). This leads to a decrease in glucose uptake and utilization. Excessive fat accumulation and abnormal lipid metabolism caused by obesity induce the transformation of macrophages from the anti-inflammatory M2 polarized state to the pro-inflammatory M1 polarized state, leading to VAT inflammation, promoting the development of obesity-related IR (Xu et al, 2003; Lumeng et al, 2007; Kojta et al, 2020). The prevention or treatment of IR and lipid metabolism disorders may be an effective way to inhibit obesityrelated diseases

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