Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK/NF-κB Signaling Pathway

• Main Authors: Madamanchi Geethangili, Chiao-Wei Lin, Harry J. Mersmann, Shih-Torng Ding
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: International Journal of Molecular Sciences
• Subjects: methyl brevifolincarboxylate; NAFLD; TG; de novo lipogenesis; lipid oxidation; inflammation
• Online Access: https://www.mdpi.com/1422-0067/22/18/10062
• ISSN: 1661-6596; 1422-0067

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 (<i>Acc1</i>), fatty acid synthase (<i>Fasn</i>) and sterol regulatory element binding protein 1c (<i>Srebp1c</i>). MBC promoted the lipid oxidation factor peroxisome proliferator activated receptor-α (<i>Pparα</i>), and its target genes, carnitine palmitoyl transferase 1 (<i>Cpt1</i>) and acyl-coenzyme A oxidase 1 (<i>Acox1</i>) 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 (<i>TNF</i>)-α, interleukin-6 (<i>IL-6</i>), <i>IL-8</i>, and <i>IL-1β</i> 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.