Activation of free fatty acid receptors, FFAR1 and FFAR4, ameliorates ulcerative colitis by promote fatty acid metabolism and mediate macrophage polarization
Copyright © 2024. Published by Elsevier B.V..
OBJECTIVE: To investigate the mechanism of action of fatty acid receptors, FFAR1 and FFAR4, on ulcerative colitis (UC) through fatty acid metabolism and macrophage polarization.
METHODS: Dextran sulfate sodium (DSS)-induced mouse model of UC mice was used to evaluate the efficacy of FFAR1 (GW9508) and FFAR4 (GSK137647) agonists by analyzing body weight, colon length, disease activity index (DAI), and histological scores. Real-time PCR and immunofluorescence analysis were performed to quantify the levels of fatty acid metabolizing enzymes and macrophage makers. FFA-induced lipid accumulation in RAW264.7 cells was visualized by Oil Red O staining analysis, and cells were collected to detect macrophage polarization by flow cytometry.
RESULTS: The combination of GW9508 and GSK137647 significantly improved DSS-induced UC symptoms, caused recovery in colon length, and decreased histological injury. GW9508 + GSK137647 treatment upregulated the expressions of CD206, lipid oxidation enzyme (CPT-1α) and anti-inflammatory cytokines (IL-4, IL-10, IL-13) but downregulated those of CD86, lipogenic enzymes (ACC1, FASN, SCD1), and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Combining the two agonists decreased FFA-induced lipid accumulation and increased CD206 expression in cell-based experiments.
CONCLUSION: Activated FFAR1 and FFAR4 ameliorates DSS-induced UC by promoting fatty acid metabolism to reduce lipid accumulation and mediate M2 macrophage polarization.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
|---|---|
| Enthalten in: |
International immunopharmacology - 130(2024) vom: 30. März, Seite 111778 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhang, Lin-Sheng [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.intimp.2024.111778 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369220226 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369220226 | ||
| 003 | DE-627 | ||
| 005 | 20240328000009.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240304s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.intimp.2024.111778 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1351.xml |
| 035 | |a (DE-627)NLM369220226 | ||
| 035 | |a (NLM)38432147 | ||
| 035 | |a (PII)S1567-5769(24)00296-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhang, Lin-Sheng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Activation of free fatty acid receptors, FFAR1 and FFAR4, ameliorates ulcerative colitis by promote fatty acid metabolism and mediate macrophage polarization |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.03.2024 | ||
| 500 | |a Date Revised 27.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a OBJECTIVE: To investigate the mechanism of action of fatty acid receptors, FFAR1 and FFAR4, on ulcerative colitis (UC) through fatty acid metabolism and macrophage polarization | ||
| 520 | |a METHODS: Dextran sulfate sodium (DSS)-induced mouse model of UC mice was used to evaluate the efficacy of FFAR1 (GW9508) and FFAR4 (GSK137647) agonists by analyzing body weight, colon length, disease activity index (DAI), and histological scores. Real-time PCR and immunofluorescence analysis were performed to quantify the levels of fatty acid metabolizing enzymes and macrophage makers. FFA-induced lipid accumulation in RAW264.7 cells was visualized by Oil Red O staining analysis, and cells were collected to detect macrophage polarization by flow cytometry | ||
| 520 | |a RESULTS: The combination of GW9508 and GSK137647 significantly improved DSS-induced UC symptoms, caused recovery in colon length, and decreased histological injury. GW9508 + GSK137647 treatment upregulated the expressions of CD206, lipid oxidation enzyme (CPT-1α) and anti-inflammatory cytokines (IL-4, IL-10, IL-13) but downregulated those of CD86, lipogenic enzymes (ACC1, FASN, SCD1), and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Combining the two agonists decreased FFA-induced lipid accumulation and increased CD206 expression in cell-based experiments | ||
| 520 | |a CONCLUSION: Activated FFAR1 and FFAR4 ameliorates DSS-induced UC by promoting fatty acid metabolism to reduce lipid accumulation and mediate M2 macrophage polarization | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Fatty acid metabolism | |
| 650 | 4 | |a Free fatty acid receptors | |
| 650 | 4 | |a Macrophage polarization | |
| 650 | 4 | |a Ulcerative colitis | |
| 650 | 7 | |a Aniline Compounds |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Dextran Sulfate |2 NLM | |
| 650 | 7 | |a 9042-14-2 |2 NLM | |
| 650 | 7 | |a Fatty Acids, Nonesterified |2 NLM | |
| 650 | 7 | |a GSK137647 |2 NLM | |
| 650 | 7 | |a GW9508 |2 NLM | |
| 650 | 7 | |a Methylamines |2 NLM | |
| 650 | 7 | |a Propionates |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a Ffar1 protein, mouse |2 NLM | |
| 650 | 7 | |a FFAR4 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
| 700 | 1 | |a Zhang, Zhi-Shou |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yu-Zhu |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Botang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiao-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Feng-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Min-Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Ping-Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Xue-Bao |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International immunopharmacology |d 2001 |g 130(2024) vom: 30. März, Seite 111778 |w (DE-627)NLM112639542 |x 1878-1705 |7 nnns |
| 773 | 1 | 8 | |g volume:130 |g year:2024 |g day:30 |g month:03 |g pages:111778 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.intimp.2024.111778 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 130 |j 2024 |b 30 |c 03 |h 111778 | ||