Orlistat, a competitive lipase inhibitor used as an antiobesity remedy, enhances inflammatory reactions in the intestine
Abstract Alterations in secondary gut metabolites derived from the microbial fermentation of food in the gut have significant effects on various aspects of host physiology. Our recent studies on obese mice treated with Orlistat, an antiobesity treatment, revealed a significantly altered gut microbial profile marked by an over-abundance of Proteobacteria and alterations in secondary gut metabolites. In this study, we determined effect of fecal metabolites from high-fat diet fed mice treated with Orlistat (HFDOrl) on colonic epithelial cells in relation to inflammation, barrier function, mitochondrial activity, reactive oxygen species (ROS) levels, and oxidative stress. Quantitative PCR was used to measure intestinal mRNA expression of oxidative stress, inflammation, apoptosis, and gut barrier function genes in mice on a high fat diet with and without Orlistat treatment versus those fed a low-fat diet (HFDOrl, HFD, Normal diet-fed [ND] respectively). Alterations to antioxidant function in HCT-116-ARE-luciferase stable cell line and mitochondrial function in Caco-2 cells was analyzed under oxidative stress with exposure to aqueous fecal extracts from HFDOrl, HFD, and ND groups. The results of this study indicate that a significant increase in anti-oxidative response was observed based on the luciferase activity of HCT-116-ARE-luciferase stable cells. Increased maximal respiration and mitochondrial ROS under oxidative stress was also detected in confluent Caco-2 cells resulting from exposure to fecal extracts from the HFDOrl group compared with the HFD group and pure Orlistat. Furthermore, mice from the HFDOrl group exhibited a significant increase in colonic epithelial expression of oxidative markers (Nrf-2 and SOD-2), inflammation-related markers (IL-6 and TNF-α), and gut barrier function markers (Muc-2 and Occludin). Taken together, the results suggest that Orlistat treatment in the HFD group causes changes in secondary gut metabolites which affect the colonic redox state and may eventually lead to the development of inflammatory, oxidative, and mitochondrial dysfunction at the cellular level..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:65 |
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| Enthalten in: |
Applied biological chemistry - 65(2022), 1 vom: 03. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Katimbwa, Dorsilla Anono [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Inflammation |
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| Anmerkungen: |
© The Author(s) 2022 |
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| doi: |
10.1186/s13765-022-00712-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC2079118749 |
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| 520 | |a Abstract Alterations in secondary gut metabolites derived from the microbial fermentation of food in the gut have significant effects on various aspects of host physiology. Our recent studies on obese mice treated with Orlistat, an antiobesity treatment, revealed a significantly altered gut microbial profile marked by an over-abundance of Proteobacteria and alterations in secondary gut metabolites. In this study, we determined effect of fecal metabolites from high-fat diet fed mice treated with Orlistat (HFDOrl) on colonic epithelial cells in relation to inflammation, barrier function, mitochondrial activity, reactive oxygen species (ROS) levels, and oxidative stress. Quantitative PCR was used to measure intestinal mRNA expression of oxidative stress, inflammation, apoptosis, and gut barrier function genes in mice on a high fat diet with and without Orlistat treatment versus those fed a low-fat diet (HFDOrl, HFD, Normal diet-fed [ND] respectively). Alterations to antioxidant function in HCT-116-ARE-luciferase stable cell line and mitochondrial function in Caco-2 cells was analyzed under oxidative stress with exposure to aqueous fecal extracts from HFDOrl, HFD, and ND groups. The results of this study indicate that a significant increase in anti-oxidative response was observed based on the luciferase activity of HCT-116-ARE-luciferase stable cells. Increased maximal respiration and mitochondrial ROS under oxidative stress was also detected in confluent Caco-2 cells resulting from exposure to fecal extracts from the HFDOrl group compared with the HFD group and pure Orlistat. Furthermore, mice from the HFDOrl group exhibited a significant increase in colonic epithelial expression of oxidative markers (Nrf-2 and SOD-2), inflammation-related markers (IL-6 and TNF-α), and gut barrier function markers (Muc-2 and Occludin). Taken together, the results suggest that Orlistat treatment in the HFD group causes changes in secondary gut metabolites which affect the colonic redox state and may eventually lead to the development of inflammatory, oxidative, and mitochondrial dysfunction at the cellular level. | ||
| 650 | 4 | |a Oxidative stress | |
| 650 | 4 | |a Mitochondrial dysfunction | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Orlistat | |
| 700 | 1 | |a Oh, Jisun |4 aut | |
| 700 | 1 | |a Jang, Chan Ho |4 aut | |
| 700 | 1 | |a Lim, Jinkyu |0 (orcid)0000-0001-6666-5759 |4 aut | |
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