Tactics with Prebiotics for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease via the Improvement of Mitophagy

Abstract

Mitophagy/autophagy plays a protective role in various forms of liver damage, by renovating cellular metabolism linking to sustain liver homeostasis. A characterized pathway for mitophagy is the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)/Parkin-dependent signaling pathway. In particular, PINK1-mediated mitophagy could play an indispensable role in improving the metabolic dysfunction-associated fatty liver disease (MAFLD) which could precede to steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. In addition, the PI3K/AKT/mTOR pathway might regulate the various characteristics of cellular homeostasis including energy metabolism, cell proliferation, and/or cell protection. Therefore, targeting mitophagy with the alteration of PI3K/AKT/mTOR or PINK1/Parkin-dependent signaling to eliminate impaired mitochondria might be an attractive strategy for the treatment of MAFLD. In particular, the efficacy of prebiotics for the treatment of MAFLD has been suggested to be useful via the modulation of the PI3K/AKT/mTOR/AMPK pathway. Additionally, several edible phytochemicals could activate mitophagy for the improvement of mitochondrial damages, which could also be a promising option to treat MAFLD with providing liver protection. Here, the potential therapeutics with several phytochemicals has been discussed for the treatment of MAFLD. Tactics with a viewpoint of prospective probiotics might contribute to the development of therapeutic interventions.

Single‐cell RNA sequencing reveals the heterogeneity and intercellular communication of hepatic stellate cells and macrophages during liver fibrosis

“…[59][60][61] By modifying or inhibiting the PI3K/AKT/mTOR pathway, various potential inhibitors, such as some natural compounds, offer the ability to prevent HSC activation and liver fibrosis. [62][63][64][65][66][67] In our study, the exogenous addition of Thbs1 to induce mouse primary HSCs activation demonstrated that Thbs1 could activate HSC by promoting this signaling pathway. In contrast, pharmacological inhibition of this pathway eliminated the effect of Thbs1 activation of HSCs.…”

“…The PI3K/AKT signaling cascade has been shown to facilitate HSC activation and collagen synthesis in response to various proproliferative and fibrotic stimuli in earlier investigations 59–61 . By modifying or inhibiting the PI3K/AKT/mTOR pathway, various potential inhibitors, such as some natural compounds, offer the ability to prevent HSC activation and liver fibrosis 62–67 . In our study, the exogenous addition of Thbs1 to induce mouse primary HSCs activation demonstrated that Thbs1 could activate HSC by promoting this signaling pathway.…”

Drug targets regulate systemic metabolism and provide new horizons to treat nonalcoholic steatohepatitis

“…Restoration of mitochondrial function by small molecules attenuates oxidative stress, and mitophagy is thus normalized. For instance, natural products (flavones) lower reactive oxygen species [ 93 ], and prebiotics improve mitophagy to ameliorate NASH [ 94 ]. Nevertheless, their benefits are mediated by non-specific mechanisms.…”

Recent Progress of Chitosan Nanoparticles for the Development of Superior Delivery of Vaccines

“…In addition, several studies have investigated the advantages of combining these natural compounds with chemotherapeutic drugs. In particular, more and more phytochemicals are now applied to the treatment of metabolic diseases [97,98]. Therefore, it might be necessary to have a more comprehensive understanding of the potential mechanisms of various diseases.…”