Polysaccharide CM1 from Cordyceps militaris hinders adipocyte differentiation and alleviates hyperlipidemia in LDLR(+/−) hamsters

Abstract

Background 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. However, lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical. Methods After 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. Results CM1, 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. Conclusions The polysaccharide CM1 lowers lipid and adipocyte differentiation by several pathways, and it has potential applications for hyperlipidemia prevention.

Structure, function and mechanism of edible fungus polysaccharides in human beings chronic diseases

“…Additionally, Craterellus cornucopioides polysaccharides showed anti-inflammatory effect by reducing the production of inflammatory mediators (iNOS) and the expression of pro-inflammatory factors (TNF-α, IL-1β and IL-18), which may be related to the inhibition of NF-κB signaling pathway (Xu et al, 2021a). For hyperlipidemia, Yu et al (2021) confirmed that Cordyceps militaris polysaccharides can alleviate hyperlipidemia by blocking preadipocyte differentiation.…”

System-level investigation of anti-obesity effects and the potential pathways of Cordyceps militaris in ovariectomized rats

“…Note that we only visualized compounds and genes related to the potential pathways monophosphate (AMP), phenylalanine, uridine, hypoxanthine, inosine, guanine, guanosine, dAMP, adenosine, adenine, cordycepin, cytosine, cytidine, uracil, hypoxanthine, 2′-deoxyguanosine, inosine, 2′-deoxyuridine, β-thymidine were detected. Among them, cordycepin is mostly considered a key component of Cordyceps species, including Cordyceps militaris [47][48][49][50]. Cordycepin binds to a number of intracellular targets, including DNA/RNA, influencing apoptosis and the cell cycle.…”

Structural Elucidation and Activities of Cordyceps militaris-Derived Polysaccharides: A Review

“…The mannan core and glycosyls in a β-configuration may play an important role in ameliorating atherosclerosis ( 105 , 106 ). Of note, the TG-lowering effect of C. militaris -derived polysaccharides is better than their TC-lowering effect ( 5 , 15 , 102 , 107 ). It is known that there is a positive correlation between plasma TG and cardiovascular disease (CVD) ( 108 , 109 ).…”

“…Furthermore, the →6)-β-D-Glc p (1→ linked glucan and the heteropolysaccharide (CM1) primarily consisting of →4)-β-D-Glc p (1→, →2)-α-D-Man p (1→, and →2,6)-α-D-Man p (1→ glycosyls, can improve cholesterol efflux in vitro ( 14 ). Recently, studies in our group demonstrated that CM1 can alleviate hyperlipidemia and adipocyte differentiation in LDLR (±) hamsters, whose lipid profiles are similar to human ( 102 ). Mechanistically, these polysaccharides are found to up-regulate genes and proteins related to RCT, such as liver X receptors and ATP-binding cassette (ABC) transporters ( 14 , 15 , 102 ).…”

“…Recently, studies in our group demonstrated that CM1 can alleviate hyperlipidemia and adipocyte differentiation in LDLR (±) hamsters, whose lipid profiles are similar to human ( 102 ). Mechanistically, these polysaccharides are found to up-regulate genes and proteins related to RCT, such as liver X receptors and ATP-binding cassette (ABC) transporters ( 14 , 15 , 102 ). Low-density lipoprotein receptor (LDLR) plays a key role in the clearance of apolipoprotein (apo) B-containing lipoproteins in circulation, and proprotein convertase subtilisin/kexin-type 9 (PCSK9) plays a key role in post-translational degradation of LDLR ( 103 ).…”