Abstract
Hepatosteatosis (HS), a clinical feature of fatty liver with the excessive intracellular accumulation of triglyceride in hepatocytes, is manifested by perturbation of the maintenance of liver lipid homeostasis. Samjunghwan (SJH) is an herbal formula used mostly in Korean traditional medicine that is effective against a number of metabolic diseases, including obesity. Herbal drugs, enriched with numerous bioactive substances, possess health-protective benefits. Meanwhile, fermented herbal products enriched with probiotics are known to improve metabolic processes. Additionally, current lines of evidence indicate that probiotics-derived metabolites, termed as postbiotics, produce the same beneficial effects as their precursors. Herein, the anti-HS effects of 5-weeks naturally fermented SJH (FSJH) was investigated with FSJH-mixed chow diet in vivo using Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats as animal models of HS and controls, respectively. In parallel, the anti-HS effects of postbiotic-metabolites of three bacterial strains [Lactobacillus brevis (LBB), Lactococcus lactis (LCL) and Lactobacillus plantarum (LBP)] isolated from FSJH were also evaluated in vitro using the FFAs-induced HepG2 cells. Feeding OLETF rats with FSJH-diet effectively reduced body, liver, and visceral adipose tissue (VAT) weights, produced marked hypolipidemic effects on serum and hepatic lipid parameters, decreased serum AST and ALT levels, and upregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR gene expressions levels. Additionally, exposure of FFAs-induced HepG2 cells to postbiotic metabolic media (PMM) of bacterial strains also produced marked hypolipidemic effects on intracellular lipid contents and significantly unregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR genes expressions levels. Overall, our results indicate that FSJH enriched with fermented metabolites could be an effective anti-HS formulation.
Highlights
Hepatosteatosis (HS), which is generally known as fatty liver, is a disease state associated with excessive intracellular deposition of lipids [ triglyceride (TG) in hepatocytes (Bradbury, 2006)]
CDNA RT PreMix was bought from Bioneer (Daejeon, South Korea), Light Cycler R FastStart DNA Master SYBR Green was acquired from Toyobo (Osaka, Japan) and radioimmuno precipitation assay (RIPA) buffer was obtained from Biosesang (Gyeonggi-do, South Korea)
A PicoGreen ds DNA assay kit was acquired from Invitrogen (Carlsbad, CA, United States), an insulin enzyme-linked immunosorbent assay (ELISA) kit was purchased from Abcam (Cambridge, United Kingdom) and TG, total cholesterol (TC), high-density lipoprotein (HDL), aspartate transaminase (AST), and alanine transaminase (ALT) kits were procured from ASAN Pharmaceutical (Seoul, South Korea)
Summary
Hepatosteatosis (HS), which is generally known as fatty liver, is a disease state associated with excessive intracellular deposition of lipids [ triglyceride (TG) in hepatocytes (Bradbury, 2006)]. Perturbation of the balance between the TG uptake/synthesis and TG hydrolysis/secretion, which is critical to the maintenance of lipid homeostasis in the liver, could be a major factor contributing to impaired lipid metabolism (Koo, 2013). The onset and progression of HS can stem from augmented free fatty acids (FFAs) uptake and de novo lipogenesis for the increased TG synthesis, as well as decreased TG hydrolysis and fatty acid beta-oxidation (Koo, 2013). HS can lead to non-alcoholic steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD), and cirrhosis, which distorts the architecture and impairs the physiological function of the liver (Farrell and Larter, 2006). The prevalence of HS has been shown to be rising at an alarming rate each year, and it is currently recognized as the most common liver disease worldwide (Bellentani, 2017)
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