Berberine ameliorates nonalcoholic fatty liver disease by decreasing the liver lipid content via reversing the abnormal expression of MTTP and LDLR

Abstract

The global incidence of nonalcoholic fatty liver disease (NAFLD) is increasing. The present study explored the effect and mechanism of berberine (BBR) on NAFLD in rats. Thirty-five Sprague-Dawley rats were randomly divided into the control and NAFLD groups, which were fed a normal diet or high-fat diet, respectively, for 8 weeks. Hematoxylin and eosin staining was performed on liver tissues and establishment of the NAFLD model was confirmed by microscopy. NAFLD rats were subsequently randomly subdivided and treated with saline or BBR for 8 weeks. The liver wet weight of rats in each group was measured, the liver tissue structure was observed by microscopy, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), fasting blood glucose (FBG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels were detected using a semi-automatic biochemical detector. Reverse transcription-quantitative PCR and western blotting were performed to determine the mRNA and protein expression levels of microsomal triglyceride transfer protein (MTTP), apolipoprotein B and low-density lipoprotein receptor (LDLR). Compared with the control group, the liver wet weight of the NAFLD rats was higher; the liver showed obvious fatty degeneration and liver TG levels increased significantly, as did serum levels of ALT, AST, TC, TG, FBG, HDL and LDL, while expression of MTTP and LDLR significantly decreased. Compared with the saline-treated NAFLD rats, the BBR-treated rats had reduced liver wet weight, improved liver steatosis and a significant decrease in liver TG levels, while ALT, AST, TC, TG, and LDL serum levels significantly decreased and MTTP levels were significantly upregulated. In conclusion, BBR treatment ameliorated the fatty liver induced by a high-fat diet in rats. Furthermore, BBR reversed the abnormal expression of MTTP and LDLR in rats with high-fat diet induced-NAFLD. The present findings suggest that fatty liver could be improved by BBR administration, via reversing the abnormal expression of MTTP and LDLR and inhibiting lipid synthesis.

Ameliorating effect of probiotic on nonalcoholic fatty liver disease and lipolytic gene expression in rabbits

“…The LDLr gene expression was lower in the HCD group than in the other groups. This result is similar to that reported by Chen et al 54 , who reported that, compared to the normal diet group, the high-fat diet group's levels of LDLr mRNA expression were considerably lower. Also, similar to Zhang et al 47 , who reported that, compared to the control group, the mRNA expression of LDLr was significantly lower in the high-fat, high-cholesterol groups.…”

Betaine Alleviates High-Fat Diet-Induced Disruptionof Hepatic Lipid and Iron Homeostasis in Mice

“…The mechanisms underlying the excessive hepatic lipid deposition in NAFLD also differ in different animal models. Some studies reported enhanced uptake of circulating lipids and de novo lipogenesis [ 15 , 38 , 39 ], while others reported impaired fatty acid oxidation and TG export [ 40 , 41 , 42 ]. Numerous studies reported contribution of hepatic up-regulation of CD36 to NAFLD pathogenesis [ 13 , 14 , 15 ].…”

It Is High Time Physicians Thought of Natural Products for Alleviating NAFLD. Is There Sufficient Evidence to Use Them?

“…All these findings were not present in the saline-treated NAFLD rats. Interestingly, BBR can cause adverse effects, including unexpected and not convenient interactions with prescription drugs, due to interference with the CYP2D6 and CYP3A4 enzymes, which are implicated in the biotransformation of endogenous compounds and xenobiotics [46,47] (Tables 1 and 2).…”