Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300-CD38 Axis
Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
|---|---|
| Enthalten in: |
Biomolecules & therapeutics - 32(2024), 2 vom: 01. März, Seite 214-223 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Song, Ji-Hye [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
CD38 |
|---|
| Anmerkungen: |
Date Revised 02.03.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.4062/biomolther.2023.061 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367873125 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367873125 | ||
| 003 | DE-627 | ||
| 005 | 20240302232514.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240201s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.4062/biomolther.2023.061 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1314.xml |
| 035 | |a (DE-627)NLM367873125 | ||
| 035 | |a (NLM)38298012 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Song, Ji-Hye |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300-CD38 Axis |
| 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 Revised 02.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CD38 | |
| 650 | 4 | |a Histone acetyltransferase | |
| 650 | 4 | |a Insulin resistance | |
| 650 | 4 | |a Robinetin | |
| 650 | 4 | |a Western diet | |
| 700 | 1 | |a Kim, Hyo-Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jangho |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Seung-Pyo |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Min-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Yu-Geun |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Jae Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Hyo-Kyoung |e verfasserin |4 aut | |
| 700 | 1 | |a Hwang, Jin-Taek |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biomolecules & therapeutics |d 2010 |g 32(2024), 2 vom: 01. März, Seite 214-223 |w (DE-627)NLM203577426 |x 1976-9148 |7 nnns |
| 773 | 1 | 8 | |g volume:32 |g year:2024 |g number:2 |g day:01 |g month:03 |g pages:214-223 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.4062/biomolther.2023.061 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 32 |j 2024 |e 2 |b 01 |c 03 |h 214-223 | ||