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Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS

Bacterial lipopolysaccharides (LPS, endotoxins) are found in high amounts in the gut lumen. LPS can cross the gut barrier and pass into the blood (endotoxemia), leading to low-grade inflammation, a common scheme in metabolic diseases. Phospholipid transfer protein (PLTP) can transfer circulating LPS...

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Autores principales: Lebrun, Lorène J., Pallot, Gaëtan, Nguyen, Maxime, Tavernier, Annabelle, Dusuel, Alois, Pilot, Thomas, Deckert, Valérie, Dugail, Isabelle, Le Guern, Naig, Pais De Barros, Jean-Paul, Benkhaled, Anissa, Choubley, Hélène, Lagrost, Laurent, Masson, David, Gautier, Thomas, Grober, Jacques
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654699/
https://www.ncbi.nlm.nih.gov/pubmed/36362012
http://dx.doi.org/10.3390/ijms232113226
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author Lebrun, Lorène J.
Pallot, Gaëtan
Nguyen, Maxime
Tavernier, Annabelle
Dusuel, Alois
Pilot, Thomas
Deckert, Valérie
Dugail, Isabelle
Le Guern, Naig
Pais De Barros, Jean-Paul
Benkhaled, Anissa
Choubley, Hélène
Lagrost, Laurent
Masson, David
Gautier, Thomas
Grober, Jacques
author_facet Lebrun, Lorène J.
Pallot, Gaëtan
Nguyen, Maxime
Tavernier, Annabelle
Dusuel, Alois
Pilot, Thomas
Deckert, Valérie
Dugail, Isabelle
Le Guern, Naig
Pais De Barros, Jean-Paul
Benkhaled, Anissa
Choubley, Hélène
Lagrost, Laurent
Masson, David
Gautier, Thomas
Grober, Jacques
author_sort Lebrun, Lorène J.
collection PubMed
description Bacterial lipopolysaccharides (LPS, endotoxins) are found in high amounts in the gut lumen. LPS can cross the gut barrier and pass into the blood (endotoxemia), leading to low-grade inflammation, a common scheme in metabolic diseases. Phospholipid transfer protein (PLTP) can transfer circulating LPS to plasma lipoproteins, thereby promoting its detoxification. However, the impact of PLTP on the metabolic fate and biological effects of gut-derived LPS is unknown. This study aimed to investigate the influence of PLTP on low-grade inflammation, obesity and insulin resistance in relationship with LPS intestinal translocation and metabolic endotoxemia. Wild-type (WT) mice were compared with Pltp-deficient mice (Pltp-KO) after a 4-month high-fat (HF) diet or oral administration of labeled LPS. On a HF diet, Pltp-KO mice showed increased weight gain, adiposity, insulin resistance, lipid abnormalities and inflammation, together with a higher exposure to endotoxemia compared to WT mice. After oral administration of LPS, PLTP deficiency led to increased intestinal translocation and decreased association of LPS to lipoproteins, together with an altered catabolism of triglyceride-rich lipoproteins (TRL). Our results show that PLTP, by modulating the intestinal translocation of LPS and plasma processing of TRL-bound LPS, has a major impact on low-grade inflammation and the onset of diet-induced metabolic disorders.
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spelling pubmed-96546992022-11-15 Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS Lebrun, Lorène J. Pallot, Gaëtan Nguyen, Maxime Tavernier, Annabelle Dusuel, Alois Pilot, Thomas Deckert, Valérie Dugail, Isabelle Le Guern, Naig Pais De Barros, Jean-Paul Benkhaled, Anissa Choubley, Hélène Lagrost, Laurent Masson, David Gautier, Thomas Grober, Jacques Int J Mol Sci Article Bacterial lipopolysaccharides (LPS, endotoxins) are found in high amounts in the gut lumen. LPS can cross the gut barrier and pass into the blood (endotoxemia), leading to low-grade inflammation, a common scheme in metabolic diseases. Phospholipid transfer protein (PLTP) can transfer circulating LPS to plasma lipoproteins, thereby promoting its detoxification. However, the impact of PLTP on the metabolic fate and biological effects of gut-derived LPS is unknown. This study aimed to investigate the influence of PLTP on low-grade inflammation, obesity and insulin resistance in relationship with LPS intestinal translocation and metabolic endotoxemia. Wild-type (WT) mice were compared with Pltp-deficient mice (Pltp-KO) after a 4-month high-fat (HF) diet or oral administration of labeled LPS. On a HF diet, Pltp-KO mice showed increased weight gain, adiposity, insulin resistance, lipid abnormalities and inflammation, together with a higher exposure to endotoxemia compared to WT mice. After oral administration of LPS, PLTP deficiency led to increased intestinal translocation and decreased association of LPS to lipoproteins, together with an altered catabolism of triglyceride-rich lipoproteins (TRL). Our results show that PLTP, by modulating the intestinal translocation of LPS and plasma processing of TRL-bound LPS, has a major impact on low-grade inflammation and the onset of diet-induced metabolic disorders. MDPI 2022-10-30 /pmc/articles/PMC9654699/ /pubmed/36362012 http://dx.doi.org/10.3390/ijms232113226 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lebrun, Lorène J.
Pallot, Gaëtan
Nguyen, Maxime
Tavernier, Annabelle
Dusuel, Alois
Pilot, Thomas
Deckert, Valérie
Dugail, Isabelle
Le Guern, Naig
Pais De Barros, Jean-Paul
Benkhaled, Anissa
Choubley, Hélène
Lagrost, Laurent
Masson, David
Gautier, Thomas
Grober, Jacques
Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS
title Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS
title_full Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS
title_fullStr Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS
title_full_unstemmed Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS
title_short Increased Weight Gain and Insulin Resistance in HF-Fed PLTP Deficient Mice Is Related to Altered Inflammatory Response and Plasma Transport of Gut-Derived LPS
title_sort increased weight gain and insulin resistance in hf-fed pltp deficient mice is related to altered inflammatory response and plasma transport of gut-derived lps
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654699/
https://www.ncbi.nlm.nih.gov/pubmed/36362012
http://dx.doi.org/10.3390/ijms232113226
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