Probiotics-rich emulsion improves insulin signalling in Palmitate/Oleate-challenged human hepatocarcinoma cells through the modulation of Fetuin-A/TLR4-JNK-NF-κB pathway
Malwina Mularczyk , Yasmina Bourebaba , Anna Kowalczuk , Krzysztof Marycz , Lynda Bourebaba
AbstractBackground Fetuin-A, also known as α2-Heremans-Schmid glycoprotein (AHSG), is an abundant plasmatic serum protein synthesized predominantly in liver and adipose tissue. This glycoprotein is known to negatively regulate insulin signaling through the inhibition of insulin receptor (IR) autophosphorylation and tyrosine kinase activity, which participates in insulin resistance (IR) and metabolic syndrome development. Recent studies demonstrated that IR and associated metabolic disorders, are closely related to the gut microbiota and modulating it by probiotics could be effective in metabolic diseases management. Objective In this present work we aimed to evaluate the effects of a probiotics-rich emulsion on reducing the IR induced by free fatty acids accumulation in human hepatocarcinoma cell line, and to elucidate the implicated molecular pathways, with a specific emphasis on the hepatokin Fetuin-A-related axis. Results Here we showed, that probiotics improve HepG2 viability, protect against apoptosis under normal and IR conditions. Moreover, the emulsion was successful in attenuating oxidative stress as well as improving mitochondrial metabolism and dynamics. Interestingly, application of the probiotics to lipotoxic HepG2 cells resulted in significant reduction of Fetuin-A/TLR4/JNK/NF-κB pathway activation, which suggests a protective effect against inflammation, obesity as well as liver related insulin resistant. Conclusion Overall, the presented data reports clearly on the potent potential of probiotics formulated in an emulsion vehicle to enhance metabolic functions of affected IR HepG2 cells, and suggest the possibility of using such preparations as insulin sensitizing therapy, playing at the same time protective role for the development of liver related insulin resistant.
|Journal series||Biomedicine & Pharmacotherapy, [Biomedicine and Pharmacotherapy], ISSN 0753-3322, e-ISSN 1950-6007, (N/A 100 pkt)|
|Publication size in sheets||0.85|
|Keywords in English||Probiotics; Insulin resistance; Lipotoxicity; Mitochondrial dysfunction; Fetuin-A; TLR4|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 19-04-2021, ArticleFromJournal|
|Publication indicators||: 2018 = 0.951; : 2019 = 4.545 (2) - 2019=4.392 (5)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.