Methyl brevifolincarboxylate attenuates free fatty acid-induced lipid metabolism and inflammation in hepatocytes through ampk/nf-κb signaling pathway
Journal
International Journal of Molecular Sciences
Journal Volume
22
Journal Issue
18
Date Issued
2021
Author(s)
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases worldwide. This study examined the potential protective effects of a naturally occurring polyphenolic compound, methyl brevifolincarboxylate (MBC) on fatty liver injury in vitro. The results showed that MBC at its non-cytotoxic concentrations, reduced lipid droplet accumulation and triglyceride (TG) levels in the oleic acid (OA)-treated human hepatocarcinoma cell line, SK-HEP-1 and murine primary hepatocytes. In OA-treated SK-HEP-1 cells and primary murine hepatocytes, MBC attenuated the mRNA expression levels of the de novo lipogenesis molecules, acetyl-coenzyme A carboxylase (Acc1), fatty acid synthase (Fasn) and sterol regulatory element binding protein 1c (Srebp1c). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (Pparα), and its target genes, carnitine palmitoyl transferase 1 (Cpt1) and acyl-coenzyme A oxidase 1 (Acox1) in both the SK-HEP-1 cells and primary murine hepatocytes. The mRNA results were further supported by the attenuated protein expression of lipogenesis and lipid oxidation molecules in OA-treated SK-HEP-1 cells. The MBC increased the expression of AMP activated protein kinase (AMPK) phosphorylation. On the other hand, MBC treatment dampened the inflammatory mediator’s, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), IL-8, and IL-1β secretion, and nuclear factor (NF)-κB expression (mRNA and protein) through reduced reactive oxygen species production in OA-treated SK-HEP-1 cells. Taken together, our results demonstrated that MBC possessed potential protective effects against NAFLD in vitro by amelioration of lipid metabolism and inflammatory markers through the AMPK/NF-κB signaling pathway. ? 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
De novo lipogenesis
Inflammation
Lipid oxidation
Methyl brevifolincarboxylate
NAFLD
TG
benzopyran derivative
fatty acid
hydroxymethylglutaryl coenzyme A reductase kinase
immunoglobulin enhancer binding protein
lipid
methyl brevifolincarboxylate
oleic acid
reactive oxygen metabolite
triacylglycerol
animal
C57BL mouse
chemistry
drug effect
human
inflammation
lipid metabolism
liver cell
male
metabolism
mouse
Phyllanthus
signal transduction
tumor cell line
AMP-Activated Protein Kinases
Animals
Benzopyrans
Cell Line, Tumor
Fatty Acids, Nonesterified
Hepatocytes
Humans
Lipid Metabolism
Lipids
Male
Mice
Mice, Inbred C57BL
NF-kappa B
Oleic Acid
Reactive Oxygen Species
Signal Transduction
Triglycerides
SDGs
Type
journal article