Anti-Obesity Effect of Chitosan Oligosaccharide Capsules (COSCs) in Obese Rats by Ameliorating Leptin Resistance and Adipogenesis

Abstract

Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a high-fat diet (HFD). After the eight-week administration of COSCs on obese rats, the body weight gain, fat/body ratio, and related biochemical indices were measured. The hepatic expressions of the leptin signal pathway (JAK2-STAT3) and gene expressions of adipogenesis-related targets were also determined. Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment.

Beneficial Metabolic Effects of Chitosan and Chitosan Oligosaccharide on Epididymal WAT Browning and Thermogenesis in Obese Rats

“…Increasing numbers of researchers are working to identify natural compounds that can stimulate browning. We previously confirmed the efficacy of CTS and its degradation product COS in the treatment of obesity and hyperlipidemia [24][25][26]. Consistent with the body weight results, we observed that the expression of the obesity-associated gene FTO was reduced in CTS-, COST-, and COSM-treated rats compared with HF rats (Supplementary Figure 2F).…”

“…Previous anti-obesity effects on COS and CTS were primarily focused on their effects on leptin resistance and fat formation [21,25,42]. Recent research reports show that browning of WAT and increased thermogenesis are effective against obesity [43,44], and there are few studies on COS and CTS in promoting WAT browning and increasing thermogenesis.…”

“…There were 50 obese rats randomly divided into the following 5 groups (n = 10 per group): The HF group (vehicle control) received a 0.9% NaCl solution via oral gavage; according to a previous study [20,25,48], the orlistat group, COST group, COSM group, and CTS group received orlistat (7 mg/kg•day), COST (600 mg/kg•day), COSM (600 mg/kg•day), CTS (600 mg/kg•day), respectively, for 8 weeks. These rats were continuously fed a HFD.…”

Chitosan Oligosaccharides Improve Glucolipid Metabolism Disorder in Liver by Suppression of Obesity-Related Inflammation and Restoration of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ)

“…To exclude unexpected accidents, we repeated these experiments more than three times independently and got consistent results. A review of the literature shows that analogous results were generated by other groups [ 12 , 27 ]. For example, in one study, COS treatment initiated less expression of proinflammatory cytokines in LPS-treated endothelial cells compared to the control group [ 27 ].…”

“…COS are known to display various bioactivities, such as anti-inflammation, anticancer, and antioxidation [ 7 , 8 , 9 ]. In addition, studies have shown that both chitosan and COS could improve overweight and dyslipidemia in rats [ 10 , 11 , 12 ]. Regretfully, the preventive effect of COS on metabolism disorder and the underlying molecular mechanism have failed to be fully elucidated.…”