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

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.

Fermented mulberry (Morus alba) leaves suppress high fat diet-induced hepatic steatosis through amelioration of the inflammatory response and autophagy pathway

“…A similar effect was observed on the amount of abdominal fat, the size of adipocytes, low-density lipoprotein (LDL) level, triglyceride level and total cholesterol (TC) level in HFD-induced obese C57BL/6N mice [32]. The anti-obesity effect of EMfCs in the liver tissue was reported to be linked to the regulation of ER stress and ER stress-induced apoptosis [34]. Therefore, above previous results about beneficial effects of EMfCs show the need for additional mechanism study related to anti-hepatic steatosis in HFD-induced obese C57BL/6N mice.…”

“…The beneficial effects of mulberry leaves have been investigated for the regulation of lipid metabolism, although there are few studies for inflammation and autophagy. Previous studies report that the extract of these leaves downregulate the lipogenesis-related genes in rats after 7 weeks treatment, and remarkably reduces the expression of the lipoprotein-related protein and accumulation of lipid in 3T3-L1 adipocytes [ 34 ]. Also, the extract of mulberry leaves induces decrease in the adipocyte differentitation in white adipose tissue of db/db mice through suppression of oxidative stress [ 41 , 42 ].…”

Auranofin Attenuates Non-Alcoholic Fatty Liver Disease by Suppressing Lipid Accumulation and NLRP3 Inflammasome-Mediated Hepatic Inflammation In Vivo and In Vitro

“…The experimental diets were purchased from Research Diets (New Brunswick, NJ, USA). The mice had an intake and daily intraperitoneal injection of normal saline and auranofin (10 mg/kg) for 8 weeks [ 35 ]. All experimental animals were acclimatized for a week, then the HFD fed and auranofin injection were started at the same time.…”

Rodent models of obesity

“…Regarding the mentioned OS, interestingly, recent data indicate that the therapeutic effects of resveratrol against hepatic steatosis of HFD obese male C57BL/6 mice are attributed to the decrease of hepatic OS, inflammation and free fatty acid uptake 47 . Likewise, Cordyceps militaris with its anti-obesity actions can be inhibited endoplasmic reticulum (ER) stress and ER stress-induced apoptosis in the hepatic steatosis of this HFD-induced obesity model 48 .…”