An In Vitro Gut–Liver–Adipose Axis Model to Evaluate the Anti-Obesity Potential of a Novel Probiotic–Polycosanol Combination

The gut-liver-adipose axis plays a pivotal role in metabolic regulation, and its dysregulation contributes to obesity and metabolic syndrome. Probiotics and polycosanol have shown potential in modulating gut barrier integrity, lipid metabolism, and inflammation. This study aimed to evaluate their co...

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Main Authors: Simone Mulè, Rebecca Galla, Francesca Parini, Mattia Botta, Sara Ferrari, Francesca Uberti
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Foods
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Online Access:https://www.mdpi.com/2304-8158/14/11/2003
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author Simone Mulè
Rebecca Galla
Francesca Parini
Mattia Botta
Sara Ferrari
Francesca Uberti
author_facet Simone Mulè
Rebecca Galla
Francesca Parini
Mattia Botta
Sara Ferrari
Francesca Uberti
author_sort Simone Mulè
collection DOAJ
description The gut-liver-adipose axis plays a pivotal role in metabolic regulation, and its dysregulation contributes to obesity and metabolic syndrome. Probiotics and polycosanol have shown potential in modulating gut barrier integrity, lipid metabolism, and inflammation. This study aimed to evaluate their combined effects using an in vitro model of the gut-liver-adipose axis. Transwell<sup>®</sup> system was used to recreate the interaction between intestinal (CaCo-2), hepatic (HepG2), and adipose (3T3-L1) cells. Cells were treated with <i>Bifidobacterium bifidum</i> GM-25, <i>Bifidobacterium infantis</i> GM-21, <i>Lacticaseibacillus rhamnosus</i> GM-28, and polycosanols. The effects were assessed by analyzing intestinal barrier integrity (TEER, tight junction proteins), hepatic and adipose lipid accumulation (Oil Red O staining), oxidative stress (ROS production, lipid peroxidation), inflammation (TNF-α) and lipid metabolism (CD36, PPARγ, AMPK and SREBP-1 levels). Probiotics and polycosanols improved intestinal integrity, increased butyrate production, and reduced ROS levels. Hepatic lipid accumulation was significantly decreased, with enhanced PPARγ and AMPK activation. In adipocytes, probiotic-polycosanols treatment suppressed SREBP-1 expression, enhanced lipid oxidation, and promoted UCP1 and PGC-1α expression, suggesting activation of thermogenic pathways. These findings underline a possible biological relevance of probiotics and polycosanols in modulating metabolic pathways, improving gut barrier integrity, and reducing inflammation, supporting their role as functional ingredients for metabolic health.
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spelling doaj-art-25bfd53765804b10a8bc800f83f72e6a2025-08-20T03:11:22ZengMDPI AGFoods2304-81582025-06-011411200310.3390/foods14112003An In Vitro Gut–Liver–Adipose Axis Model to Evaluate the Anti-Obesity Potential of a Novel Probiotic–Polycosanol CombinationSimone Mulè0Rebecca Galla1Francesca Parini2Mattia Botta3Sara Ferrari4Francesca Uberti5Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale (UPO), 13100 Vercelli, ItalyDepartment for Sustainable Development and Ecological Transition, University of Piemonte Orientale (UPO), 13100 Vercelli, ItalyDepartment for Sustainable Development and Ecological Transition, University of Piemonte Orientale (UPO), 13100 Vercelli, ItalyDepartment for Sustainable Development and Ecological Transition, University of Piemonte Orientale (UPO), 13100 Vercelli, ItalyDepartment for Sustainable Development and Ecological Transition, University of Piemonte Orientale (UPO), 13100 Vercelli, ItalyNoivita Srls, Spin Off, University of Piemonte Orientale (UPO), Via Solaroli 17, 28100 Novara, ItalyThe gut-liver-adipose axis plays a pivotal role in metabolic regulation, and its dysregulation contributes to obesity and metabolic syndrome. Probiotics and polycosanol have shown potential in modulating gut barrier integrity, lipid metabolism, and inflammation. This study aimed to evaluate their combined effects using an in vitro model of the gut-liver-adipose axis. Transwell<sup>®</sup> system was used to recreate the interaction between intestinal (CaCo-2), hepatic (HepG2), and adipose (3T3-L1) cells. Cells were treated with <i>Bifidobacterium bifidum</i> GM-25, <i>Bifidobacterium infantis</i> GM-21, <i>Lacticaseibacillus rhamnosus</i> GM-28, and polycosanols. The effects were assessed by analyzing intestinal barrier integrity (TEER, tight junction proteins), hepatic and adipose lipid accumulation (Oil Red O staining), oxidative stress (ROS production, lipid peroxidation), inflammation (TNF-α) and lipid metabolism (CD36, PPARγ, AMPK and SREBP-1 levels). Probiotics and polycosanols improved intestinal integrity, increased butyrate production, and reduced ROS levels. Hepatic lipid accumulation was significantly decreased, with enhanced PPARγ and AMPK activation. In adipocytes, probiotic-polycosanols treatment suppressed SREBP-1 expression, enhanced lipid oxidation, and promoted UCP1 and PGC-1α expression, suggesting activation of thermogenic pathways. These findings underline a possible biological relevance of probiotics and polycosanols in modulating metabolic pathways, improving gut barrier integrity, and reducing inflammation, supporting their role as functional ingredients for metabolic health.https://www.mdpi.com/2304-8158/14/11/2003lipid buildupadipocyte metabolismnutraceutical approachnovel combinationbrowning processoral supplementation
spellingShingle Simone Mulè
Rebecca Galla
Francesca Parini
Mattia Botta
Sara Ferrari
Francesca Uberti
An In Vitro Gut–Liver–Adipose Axis Model to Evaluate the Anti-Obesity Potential of a Novel Probiotic–Polycosanol Combination
Foods
lipid buildup
adipocyte metabolism
nutraceutical approach
novel combination
browning process
oral supplementation
title An In Vitro Gut–Liver–Adipose Axis Model to Evaluate the Anti-Obesity Potential of a Novel Probiotic–Polycosanol Combination
title_full An In Vitro Gut–Liver–Adipose Axis Model to Evaluate the Anti-Obesity Potential of a Novel Probiotic–Polycosanol Combination
title_fullStr An In Vitro Gut–Liver–Adipose Axis Model to Evaluate the Anti-Obesity Potential of a Novel Probiotic–Polycosanol Combination
title_full_unstemmed An In Vitro Gut–Liver–Adipose Axis Model to Evaluate the Anti-Obesity Potential of a Novel Probiotic–Polycosanol Combination
title_short An In Vitro Gut–Liver–Adipose Axis Model to Evaluate the Anti-Obesity Potential of a Novel Probiotic–Polycosanol Combination
title_sort in vitro gut liver adipose axis model to evaluate the anti obesity potential of a novel probiotic polycosanol combination
topic lipid buildup
adipocyte metabolism
nutraceutical approach
novel combination
browning process
oral supplementation
url https://www.mdpi.com/2304-8158/14/11/2003
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