Lab Anim Res.  2018 Dec;34(4):288-294. 10.5625/lar.2018.34.4.288.

Inhibition of endoplasmic reticulum stress in high-fat-diet-induced obese C57BL/6 mice: Efficacy of a novel extract from mulberry (Morus alba) leaves fermented with Cordyceps militaris

• Lee MR
• Bae SJ
• Kim JE
• Song BR
• Choi JY
• Park JJ
• Park JW
• Kang MJ
• Choi HJ
• Choi YW
• Kim KM
• Hwang DY

• KMID: 2459307
• DOI: http://doi.org/10.5625/lar.2018.34.4.288

Abstract

A few clues about correlation between endoplasmic reticulum (ER) stress and mulberry (Morus alba) leaves were investigated in only the experimental autoimmune myocarditis and streptozotocin-induced diabetes. To investigate whether a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) could suppress ER in fatty liver, alterations in the key parameters for ER stress response were measured in high fat diet (HFD)-induced obese C57L/6 mice treated with EMfC for 12 weeks. The area of adipocytes in the liver section were significantly decreased in the HFD+EMfC treated group as compared to the HFD+Vehicle treated group, while their level was higher in HFD+Vehicle treated group than No treated group. The level of the eukaryotic initiation factor 2 alpha (eIF2α) and inositol-requiring enzyme 1 beta (IRE1α) phosphorylation and CCAAT-enhancer-binding protein homologous protein (CHOP) expression were remarkably enhanced in the HFD+Vehicle treated group. However, their levels were restored in the HFD+EMfC treated group, although some differences were detected in the decrease rate. Similar recovery was observed on the ER stress-induced apoptosis. The level of Caspase-3, Bcl-2 and Bax were decreased in the HFD+EMfC and HFD+orlistat (OT) treated group compared to the HFD+Vehicle treated group. The results of the present study therefore provide first evidence that EMfC with the anti-obesity effects can be suppressed ER stress and ER stress-induced apoptosis in the hepatic steatosis of HFD-induced obesity model.

Keyword

Mulberry leaf; ER stress response; fatty liver; apoptosis

MeSH Terms

Adipocytes
Animals
Apoptosis
Caspase 3
CCAAT-Enhancer-Binding Proteins
Cordyceps*
Diet, High-Fat
Endoplasmic Reticulum Stress*
Endoplasmic Reticulum*
Eukaryotic Initiation Factor-2
Fatty Liver
Liver
Mice*
Morus*
Myocarditis
Obesity
Phosphorylation
CCAAT-Enhancer-Binding Proteins
Caspase 3
Eukaryotic Initiation Factor-2

Figure

• 

  Figure 1 Measurement of fat accumulation in the liver tissue. (A) After the collection and staining of the liver tissue from the No, HFD+Vehicle, HFD+OT or HFD+EMfC treated group in C57BL/6 mice, their histological structure were observed at 400× magnifications using a light microscope. (B) Area of accumulated fat is presented as relative levels. Data represents the mean±SD from three replicates. *P<0.05 compared to the No treated group. #P<0.05 compared to the HFD+Vehicle treated group.

• 

  Figure 2 Expression of key marker proteins for ER stress. The expression levels of eIF2α, p-eIF2α, CHOP, p-IRE1α and IRE1α in total proteins were detected with specific antibodies. The level of β-actin is also shown as an endogenous control. The band intensity of these proteins was determined using an imaging densitometer, and the relative levels of each protein were calculated based on the intensity of actin protein as an endogenous control. Data represent the means±SD from three replicates. *P<0.05 compared to the No treated group. #P<0.05 compared to the HFD+Vehicle treated group.

• 

  Figure 3 Expression of key marker proteins for ER stress-induced apoptosis. The expression levels of Caspase-3, Bcl-2 and Bax in total proteins were detected with specific antibodies. The level of β-actin is also shown as an endogenous control. The band intensity of the proteins was determined using an imaging densitometer, and the relative levels of each protein were calculated based on the intensity of actin protein as an endogenous control. Data represent the means±SD from three replicates. *P<0.05 compared to the No treated group. #P<0.05 compared to the HFD+Vehicle treated group.

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