Ferulic Acid Prevents Nonalcoholic Fatty Liver Disease by Promoting Fatty Acid Oxidation and Energy Expenditure in C57BL/6 Mice Fed a High-Fat Diet

Abstract

There is a consensus that ferulic acid (FA), the most prominent phenolic acid in whole grains, displays a protective effect in non-alcoholic fatty liver disease (NAFLD), though its underlying mechanism not fully elucidated. This study aimed to investigate the protective effect of FA on high-fat diet (HFD)-induced NAFLD in mice and its potential mechanism. C57BL/6 mice were divided into the control diet (CON) group, the HFD group, and the treatment (HFD+FA) group, fed with an HFD and FA (100 mg/kg/day) by oral gavage for 12 weeks. Hematoxylin and eosin (H&E) staining and Oil Red O staining were used to evaluate liver tissue pathological changes and lipid accumulation respectively. It was demonstrated that FA supplementation prevented HFD-induced NAFLD, which was evidenced by the decreased accumulation of lipid and hepatic steatosis in the HFD+FA group. Specifically, FA supplementation decreased hepatic triacylglycerol (TG) content by 33.5% (p < 0.01). Metabolic cage studies reveal that FA-treated mice have elevated energy expenditure by 11.5% during dark phases. Mechanistically, FA treatment increases the expression of rate-limiting enzymes of fatty acid oxidation and ketone body biosynthesis CPT1A, ACOX1 and HMGCS2, which are the peroxisome proliferator-activated receptors α (PPARα) targets in liver. In conclusion, FA could effectively prevent HFD-induced NAFLD possibly by activating PPARα to increase energy expenditure and decrease the accumulation of triacylglycerol in the liver.

Ferulic acid attenuates high-fat diet-induced hypercholesterolemia by activating classic bile acid synthesis pathway

“…The murine liver tissue sections were prepared as described in Luo et al ( 20 ). For immunohistochemistry (IHC) staining, the samples were incubated with antibodies against CYP7A1 (1:50 dilution; Solarbio Technology Co., Ltd., Beijing, China).…”

“…Preparation of mouse liver tissue lysate and western blot analysis were as previously described ( 20 ). The difference is that the PVDF membranes were incubated overnight at 4°C with the antibody against CYP7A1 followed by the secondary antibody (Solarbio Technology Co., Ltd., Beijing, China).…”

A Comprehensive Review of Health-Benefiting Components in Rapeseed Oil

“…It was also reported that FA could ameliorate aflatoxin B1-induced duodenal barrier damage in rats [ 142 ]. FA effectively prevents high-fat diet-induced fatty liver disease by activating the PPARα signaling pathway to decrease the accumulation of triacylglycerol in the liver and increase the consumption of energy [ 143 ]. FA acid has a cardioprotective effect induced by severe endoplasmic reticulum stress [ 144 ].…”

Human diet‐derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization

“…Furthermore, an initial evaluation of ferulic acid's anticancer activity in HepG2 cells demonstrated its role in inhibiting tumor cell proliferation through inducing apoptosis and autophagy . High-fructose-induced hyperuricemia and NAFLD C1q /CTRP3(+)/ACL(-) (Elseweidy et al, 2022) Ferulic acid Cecal ligation and perforation (CLP)-induced and lipopolysaccharide (LPS)-induced ALI GSK-3β/CREB/ NF-κB(-) (Cao et al, 2021) Aflatoxin B1-induced liver damage CYP450(-)/Nrf2/GST(+) (Wang, He, et al, 2021) CCl4-induced hepatic fibrosis TGF-β1/ Smads(-) (Mu et al, 2018) HCHF-induced NASH ROCK/NF-κB(-) (Wei et al, 2021) HFD-induced NAFLD PPARα(+) (Luo et al, 2022) Chlorogenic acid CCl4-induced liver fibrosis and inflammation TLR4/MyD88/NF-κB(-) (Shi et al, 2013) ANIT-induced liver injury STAT3/NF-κB(-) (Tan et al, 2016) CCl4-induced liver injury NLRP3(-)/Nrf2(+) (Shi et al, 2018) HFD-induced NAFLD TLR4(-) (Shi et al, 2021) MCDD diet-induced NAFLD LPS-TLR4-MyD88(-) (Gu et al, 2023) MCD diet-induced NAFLD ECM/HSCs(-) (Miao et al, 2022) HCC cells Hep-G2 and Huh-7 NF-κB(-)/BBC3(+) (Jiang et al, 2021) Gallic acid aHSCs TRADD/RIP3(+) (Chang et al, 2015) HFD-induced NAFLD rats and palmitic acid (PA) and oleic acid (OA)-treated hepatocytes AMPK/ACC/PPARα(-) (J. Fructose-induced NAFLD AMPK/SREBP-1/ ACC/ FASN axis (-) (Lu et al, 2023)…”

“…Additionally, ferulic acid exhibited anti‐inflammatory effects in rats with NASH by inactivating the ROCK/NF‐κB signaling pathway (Wei et al, 2021). A recent study reported that ferulic acid promotes fatty acid oxidation by activating the PPARα signaling pathway in high‐fat‐diet‐induced NAFLD mice (Luo et al, 2022). Furthermore, an initial evaluation of ferulic acid's anticancer activity in HepG2 cells demonstrated its role in inhibiting tumor cell proliferation through inducing apoptosis and autophagy (Wang et al, 2022).…”