The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

Abstract

The objective of this study was to investigate the effects of simvastatin (SIM) on lipid metabolism disorders and gut microbiota in high-fat diet-induced hyperlipidemic rats. The obtained results revealed that feeding rats with SIM (20 mg/kg/day) significantly decreased serum lipid level and inhibited hepatic lipid accumulation and steatosis. Histological analysis further indicated that SIM reduced lipid deposition in adipocytes and hepatocytes in comparison with that of the HFD group. The underlying mechanisms of SIM administration against HFD-induced hyperlipidemia were also studied by UPLC-Q-TOF/MS-based liver metabonomics coupled with pathway analysis. Metabolic pathway enrichment analysis of liver metabolites with significant difference in abundance indicated that fatty acids metabolism and amino acid metabolism were the main metabolic pathways altered by SIM administration. Meanwhile, operational taxonomic units (OTUs) analysis revealed that oral administration of SIM altered the composition of gut microbiota, including Ruminococcaceae (OTU960) and Lactobacillus (OTU152), and so on. Furthermore, SIM treatment also regulated the mRNA levels of the genes involved in lipid and cholesterol metabolism. Immunohistochemistry (IHC) analysis of the liver-related proteins (CD36, CYP7A1 and SREBP-1C) showed that oral administration of SIM could regulate the levels of the protein expression related to hepatic lipid metabolism.

High-Fat Diets-Induced Metabolic Disorders to Study Molecular Mechanism of Hyperlipidemia in Rats

“…Hyperlipidemia is the cause of CHD and other cardiovascular diseases (CVD) (3). As reported previously, it was shown that long-term or chronic administration of HFD in rats could induce a significant increase in TC, TG, LDL-C, and VLDL-C compared to the control group, while HDL-C decreased (13,28,29). Based on Table 3, lipid profile parameters showed no significant changes at the beginning of HFD treatment.…”

Ferulic Acid Ameliorates Atherosclerotic Injury by Modulating Gut Microbiota and Lipid Metabolism

“…Analysis at deeper taxonomic level showed that FA decreased the relative abundance of Erysipelotrichaceae, which is positively associated with host lipid deposition ( Kaakoush, 2015 ). Furthermore, FA also increased the relative abundance of a health-associated family, Ruminococcaceae , which promotes intestinal health and decreases the level of triacylglycerols, phospholipids and cholesteryl esters in mice ( Zhang et al, 2020 ). At the genus level, FA treatment significantly decreased the relative abundance of Ileibacterium , which protects mice from adiposity ( den Hartigh et al, 2018 ).…”

Effects of Lactobacillus plantarum FZU3013-Fermented Laminaria japonica on Lipid Metabolism and Gut Microbiota in Hyperlipidaemic Rats

“…Fresh liver or adipose tissue samples were fixed in formalin solution (4%) overnight. Tissue sections (5 μm) were prepared, stained with haematoxylin and eosin ( 5 ), and examined under light microscopy (Bresser, Borken, Germany).…”

“…Hyperlipidaemia is linked to the development of cardiovascular diseases, resulting in non-alcoholic fatty liver (NAFL) to a certain extent, and this has received considerable critical attention (1)(2)(3)(4). The main treatment for hyperlipidaemia is drug therapy, which often leads to various adverse reactions (5). Currently, researchers are focusing their attention on food therapy to prevent hyperlipidaemia because of its high efficacy complemented with few or no side effects.…”