Abstract

BackgroundCordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects. However, lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical.MethodsAfter 5 months, the hamsters were weighed and sampled under anesthesia after overnight fasting. The lipid-lowering effect and mechanisms of the polysaccharide CM1 was investigated by cellular and molecular technologies. Furthermore, the effect of the polysaccharide CM1 (100 μg/mL) on inhibiting adipocyte differentiation was investigated in vitro.ResultsCM1, a polysaccharide from C. militaris, significantly decreased plasma total cholesterol, triglyceride and epididymal fat index in LDLR(+/−) hamsters, which have a human-like lipid profile. After 5 months’ administration, CM1 decreased the plasma level of apolipoprotein B48, modulated the expression of key genes and proteins in liver, small intestine, and epididymal fat. CM1 also inhibited preadipocyte differentiation in 3T3-L1 cells by downregulating the key genes involved in lipid droplet formation.ConclusionsThe polysaccharide CM1 lowers lipid and adipocyte differentiation by several pathways, and it has potential applications for hyperlipidemia prevention.

Highlights

  • Cordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects

  • This study suggested that CM1 can lower TG by upregulating PPARα-mediated β-oxidation and lipoprotein lipase (LPL)-mediated lipoprotein degradation in the liver

  • The limitations of this study are listed below. (1), as CM1 reduced the expression of Niemann-Pick C1-like 1 (NPC1L1) protein, whether this polysaccharide can inhibit intestinal cholesterol absorption is an interesting question and should be answered in future studies. (2), genes exert their functions after being translated to the corresponding. This long-term study demonstrated for the first time that the polysaccharide CM1 from the fruiting body of C. militaris has an attractive effect on lowering hyperlipidemia in low-density lipoprotein receptor (LDLR)(+/−) hamsters via influencing on multiple pathways

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Summary

Introduction

Cordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects. Lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical. Hyperlipidemia is a pathogenic factor for cardiovascular disease (CVD) [1,2,3]. Cholesterol-lowering drugs, such as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies, play important roles in prevention and treatment of CVD [1,2,3]. The currently deployed lipid-lowering drugs are unable to completely retard the progression of CVD. The edible fungus Cordyceps militaris is a commercialized mushroom that primarily consumed in Asian Significant research has been conducted aimed at utilizing natural compounds in food for the same purposes, due to their potentially lower toxicity levels.

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