Cordycepin reduces weight through regulating gut microbiota in high-fat diet-induced obese rats

Abstract

Background: An increasing number of studies have shown that obesity is the key etiological agent of cardiovascular diseases, nonalcoholic fatty liver disease, type 2 diabetes and several kinds of cancer and that gut microbiota change was one of the reasons suffering from obesity. At present, the gut microbiota has gained increased attention as a potential energy metabolism organ. Our recent study reported that cordycepin, a major bioactive component separated from Cordyceps militaris, prevented body weight gain in mice fed a high-fat diet directly acting to adipocytes, however, the effect of cordycepin regulating gut microbiota keeps unknown.

Methods: In this research, we synthesized cordycepin (3-deoxyadenosine) by chemical methods and verified that cordycepin reduces body weight gain and fat accumulation around the epididymis and the kidneys of rats fed a high-fat diet. Furthermore, we used high-throughput sequencing on a MiSeq Illumina platform to test the species of intestinal bacteria in high-fat-diet-induced obese rats.

Results: We found that cordycepin modifies the relative abundance of intestinal bacteria in high-fat-diet-induced obese rats. However, cordycepin did not alter the variety of bacteria in the intestine. Cordycepin treatment dramatically reversed the relative abundance of two dominant bacterial phyla (Bacteroidetes and Firmicutes) in the high-fat-diet-induced obese rats, resulting in abundance similar to that of the chow diet group.

Conclusion: Our study suggests that cordycepin can reduce body weight and microbiome done by cordycepin seems be a result among its mechanisms of obesity reduction.

Keywords: Body weight; Cordycepin; Fat; Gut microbiota; Obesity.

Fig. 1

Synthetic route and chemical structure of cordycepin. (I) Cordycepin. (II, III, IV) intermediate products

Fig. 2

Anti-obesity effects of cordycepin in high-fat-diet-induced obese rats. (a) Body weight. (b) Adiposity index, calculated according to the following formula: 100 × (epididymal fat weight + perirenal fat weight)/body weight. Differences were assessed by one-way ANOVA, (*P < 0.05, **P < 0.01, ***P < 0.001). NFD means the rats were fed a normal diet; HFD meansthe rats were fed a high-fat diet; CCS means the rats were fed a high-fat diet and received cordycepin (50 mg/kg) for 4 weeks continuously

Fig. 3

Diversity and richness of the gut microbiota in rats. (a) Displays the rarefaction curves of samples from the NFD group, HFD group and CCS group. (b) Displays the Shannon index of samples from the NFD group, HFD group and CCS group. (c) PCoA plot. Principal component analysis (PCA) scores plot of gut microbiota based on the relative abundance of OTUs. (d) Cluster analysis, unweighted uniFrac-OTU table. NFD means that the rats were fed a normal diet (n = 3), HFD meansthe rats were fed a high-fat diet (n = 3), and CCS meansthe rats were fed a high-fat diet and received cordycepin (50 mg/kg) (n = 3) for 4 weeks continuously

Fig. 4

Composition analysis of gut microbiota at different taxonomic levels among all samples. (a) Phylum. (b) Class. (c) Order. (d) Family. (e) Genus. (f) Species. Only the top 20 most abundant OTUs are displayed. NFD means that the rats were fed a normal diet (n = 3), HFD meansthe rats were fed a high-fat diet (n = 3), and CCS means the rats were fed a high-fat diet and received cordycepin (50 mg/kg) (n = 3) for 4 weeks continuously

Fig. 5

Heatmap analysis of gut microbiota changes from different treatments. (a) Phylum. (b) Class.The color intensity in each sample is normalized to represent its relative ratio in the three groups. A range of colors, from blue to red, indicates the relative values of microbiota (0–4). NFD means that the rats were fed a normal diet (n = 3), HFD meansthe rats were fed a high-fat diet (n = 3), and CCS meansthe rats were fed a high-fat diet andreceived cordycepin (50 mg/kg) (n = 3)for 4 weeks continuously