Fermented Cordyceps militaris Extract Prevents Hepatosteatosis and Adipocyte Hypertrophy in High Fat Diet-Fed Mice

Abstract

Nonalcoholic fatty liver diseases (NAFLD) is characterized by accumulation of lipid droplets in the liver. The objective of this study was to evaluate protective effects of fermented Cordyceps militaris extract by Pediococcus pentosaceus ON188 (ONE) against hepatosteatosis and obesity in mice fed a high-fat diet (HFD). Eight-week-old male C57BL/6J mice were fed HFD mixed with ONE for four weeks and its effects on hepatosteatosis and obesity were examined. Although ONE did not change food intake, it reduced body weights of mice at administration dose of 200 mg/kg/day. Activities of lactate dehydrogenase (LDH), aspartate transaminase (AST), and alanine transaminase (ALT) as plasma parameters were reduced by ONE in a dose-dependent manner. Hepatic lipid droplets and triglyceride (TG) levels were also reduced by ONE due to upregulation of fatty acid oxidizing genes such as carnithine palmitoyltransferase (CPT1) and peroxisomal proliferator activated receptor α(PPARα) mediated by induction of sphingosine kinase 2 (SPHK2). In epididymal fat tissue, sizes of adipocytes were significantly reduced by ONE in a dose-dependent manner. This is mainly due to suppression of lipogenesis and upregulation of adipocyte browning genes. Collectively, these results suggest that fermented ONE can activate fatty acid oxidation via SPHK2 in the liver. It can also suppress lipogenesis and activate browning in adipose tissue. Thus, ONE might have potential to be used for the development of functional foods against liver dysfunction and obesity.

Protective Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract against Hepatic Steatosis in High Fat Diet‐Induced Nonalcoholic Fatty Liver Disease Mice

“…Hepatic steatosis, the first hallmark of NAFLD, is known to be characterized by excessive accumulation of lipid in hepatocytes [52]. Several previous studies have provided evidence regarding the hepatoprotective properties against HFD-induced NAFLD by reducing the liver damage markers and inhibiting the accumulation of lipid droplets in the liver tissues of HFD-fed rodents [53,54]. In parallel, our results demonstrated that ALM16 can exert protective effects and synergistic action against hepatic steatosis and liver injury in HFD-fed mice.…”

<p>The Mechanism of Traditional Chinese Medicine for the Treatment of Obesity</p>

“…27 Resveratrol (Polygonum cuspidatum) and the extract from fermented Cordyceps militaris decrease the expression and activity of SREBP-1c and decrease fat synthesis. 28,29 Curcumin increases the phosphorylation of acetyl-CoA carboxylase (p-ACC) and decreases the ratelimiting enzyme acetyl-CoA carboxylase (ACC) of fatty acid synthesis, which inhibits lipogenesis. 30 Traditional Chinese medicine can also inhibit lipid synthesis and metabolism by activating AMPK.…”

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

“…The water extracts or polysaccharides of the Cordyces species have anti-hyperlipidemic effects in mice [ 10 – 13 ]. However, the lipid profile in mice is distinct from humans [ 25 ].…”

“…A previous study already demonstrated that CM1 may improve HDL-mediated cholesterol efflux [ 17 ]. Recent studies also indicated that water-soluble components of Cordyceps species can lower hyperlipidemia [ 10 – 13 , 39 ]. This study suggested that CM1 is one of the water-soluble components with hypolipidemic effects.…”

“…Thirdly, CM1 may inhibit adipocyte differentiation in LDLR (+/−) hamsters. A previous study demonstrated that the fermented C. militaris extract can inhibit adipocyte hypertrophy in mice [ 13 ]. As PPARγ is a major activator of adipocyte differentiation [ 49 ], the inhibitory effect of CM1 on the adipose of the LDLR (+/−) hamster can be partially attributed to its downregulation of PPARγ.…”