Liensinine alleviates high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) through suppressing oxidative stress and inflammation via regulating TAK1/AMPK signaling

Jan 9, 2022International immunopharmacology

Liensinine may reduce fatty liver disease caused by a high-fat diet by lowering oxidative stress and inflammation through TAK1/AMPK signaling

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Liensinine (LIEN) significantly reduced lipid deposition in palmitate acid-treated cells by enhancing AMPK activation.

LIEN treatment improved AMPK activation and decreased lipid accumulation in liver cells exposed to fatty acids.
LIEN strongly reduced the generation of harmful reactive oxygen species (ROS) in these cells by promoting Nrf2 activity.
The inflammatory response triggered by palmitate acid was notably inhibited by LIEN through blocking the TAK1/NF-κB signaling pathway.
LIEN's effects on reducing ROS, lipid disorder, and inflammation were primarily linked to its activation of AMPK and repression of TAK1.
In vivo studies showed that LIEN improved metabolic disorders and inflammation in mice fed a high-fat diet.

AI simplified

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases without effective pharmacological intervention. Liensinine (LIEN), a plant-derived isoquinoline alkaloid, exerts key roles in regulating various cellular processes. However, its potential on NAFLD progression has not been reported. In the study, we attempted to explore the regulatory effects of LIEN on fatty liver, and the underlying molecular mechanisms. Our in vitro experiments showed that LIEN treatments significantly reduced the lipid deposition in palmitate acid (PA)-treated cells by improving AMP-activated protein kinase (AMPK) activation. Additionally, excessive reactive oxygen species (ROS) generation was also strongly down-regulated by LIEN in cells upon PA stimulation through enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation. Moreover, PA-triggered inflammatory response was markedly restrained by LIEN via the blockage of TGF-β-activating kinase 1/nuclear factor-κB (TAK1/NF-κB) signaling. Intriguingly, we further found that LIEN-prohibited ROS production, lipid disorder and inflammation were largely dependent on AMPK activation through repressing TAK1. Consistently, our in vivo experiments confirmed that LIEN treatments efficiently improved the metabolic disorder, insulin resistance, dyslipidemia in high fat diet (HFD)-fed mice. Furthermore, HFD-triggered oxidative stress and inflammation in liver were greatly meliorated by LIEN administration by mediating Nrf2 and TAK1 signaling pathways, respectively. Collectively, all these findings demonstrated that LIEN exerted anti-dyslipidemia, anti-oxidant and anti-inflammatory effects to alleviate NAFLD progression mainly through modulating TAK1/AMPK signaling, and thus could be considered as a promising therapeutic strategy.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Liensinine alleviates high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) through suppressing oxidative stress and inflammation via regulating TAK1/AMPK signaling

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief