Reduced expression of peroxisome proliferator-activated receptor-alpha may have an important role in the development of non-alcoholic fatty liver disease
Copyright 2004 Blackwell Publishing Asia Pty Ltd.
BACKGROUND: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains poorly understood, metabolic syndrome associated with insulin resistance is the most reproducible factor in the development of NAFLD. Fat accumulation in hepatocytes results from an imbalance in the input, output and oxidation of fatty acid. Peroxisomes contain a battery of fatty acid oxidizing enzymes, the first of which, acyl-CoA oxidase (AOX), initiates the beta-oxidation spiral. One of the mammalian peroxisome proliferator-activated receptors (PPAR), PPAR-alpha, regulates the transcriptional expression of the enzymes involved in fatty acid beta-oxidation. The aim of the present study was to define the role of PPAR-alpha and AOX in the development of NAFLD using the Otsuka Long-Evans Tokushima fatty (OLETF) rat model.
METHODS: Liver tissue from OLETF (n = 12) and control (n = 10) rats 12, 28, and 40 weeks old were processed for histopathological and western blot analysis. The messenger RNA of PPAR-alpha and AOX were quantified by real-time RT-PCR.
RESULTS: At 40 weeks old, the histological analysis of the OLETF rat liver had steatosis (approximately 66%) and mild inflammation, which were comparable to those in NAFLD. Histological changes were unremarkable in 12 week and 28 week rats. In 12 week OLETF rats, the mRNA of AOX was 63% of the control. Expression of PPAR-alpha mRNA was also reduced to 3% that of the control. Along with the changes of mRNA, the protein expression of PPAR-alpha was also significantly reduced to 17% that of the control. In 28 week and 40 week animals, PPAR-alpha protein expression gradually increased to 75% and 78% that of the control. Expression of PPAR-alpha mRNA was also increased by up to 26% and 110% of the control. AOX, regulated by PPAR-alpha, also increased to 149% and 120% of the control.
CONCLUSION: Reduced expression of PPAR-alpha and AOX was observed even before definite steatosis had developed. The alteration of peroxisomal fatty acid metabolism may have an important role in the development of NAFLD.
| Errataetall: |
CommentIn: J Gastroenterol Hepatol. 2004 Dec;19(12):1335-7. - PMID 15610304 |
|---|---|
| Medienart: |
Artikel |
| Erscheinungsjahr: |
2004 |
|---|---|
| Erschienen: |
2004 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
Journal of gastroenterology and hepatology - 19(2004), 7 vom: 01. Juli, Seite 799-804 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yeon, Jong Eun [VerfasserIn] |
|---|
| Themen: |
Acyl-CoA Oxidase |
|---|
| Anmerkungen: |
Date Completed 30.11.2004 Date Revised 15.11.2006 published: Print CommentIn: J Gastroenterol Hepatol. 2004 Dec;19(12):1335-7. - PMID 15610304 Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM148961037 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM148961037 | ||
| 003 | DE-627 | ||
| 005 | 20231223050719.0 | ||
| 007 | tu | ||
| 008 | 231223s2004 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0497.xml |
| 035 | |a (DE-627)NLM148961037 | ||
| 035 | |a (NLM)15209628 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yeon, Jong Eun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Reduced expression of peroxisome proliferator-activated receptor-alpha may have an important role in the development of non-alcoholic fatty liver disease |
| 264 | 1 | |c 2004 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 30.11.2004 | ||
| 500 | |a Date Revised 15.11.2006 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: J Gastroenterol Hepatol. 2004 Dec;19(12):1335-7. - PMID 15610304 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright 2004 Blackwell Publishing Asia Pty Ltd | ||
| 520 | |a BACKGROUND: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains poorly understood, metabolic syndrome associated with insulin resistance is the most reproducible factor in the development of NAFLD. Fat accumulation in hepatocytes results from an imbalance in the input, output and oxidation of fatty acid. Peroxisomes contain a battery of fatty acid oxidizing enzymes, the first of which, acyl-CoA oxidase (AOX), initiates the beta-oxidation spiral. One of the mammalian peroxisome proliferator-activated receptors (PPAR), PPAR-alpha, regulates the transcriptional expression of the enzymes involved in fatty acid beta-oxidation. The aim of the present study was to define the role of PPAR-alpha and AOX in the development of NAFLD using the Otsuka Long-Evans Tokushima fatty (OLETF) rat model | ||
| 520 | |a METHODS: Liver tissue from OLETF (n = 12) and control (n = 10) rats 12, 28, and 40 weeks old were processed for histopathological and western blot analysis. The messenger RNA of PPAR-alpha and AOX were quantified by real-time RT-PCR | ||
| 520 | |a RESULTS: At 40 weeks old, the histological analysis of the OLETF rat liver had steatosis (approximately 66%) and mild inflammation, which were comparable to those in NAFLD. Histological changes were unremarkable in 12 week and 28 week rats. In 12 week OLETF rats, the mRNA of AOX was 63% of the control. Expression of PPAR-alpha mRNA was also reduced to 3% that of the control. Along with the changes of mRNA, the protein expression of PPAR-alpha was also significantly reduced to 17% that of the control. In 28 week and 40 week animals, PPAR-alpha protein expression gradually increased to 75% and 78% that of the control. Expression of PPAR-alpha mRNA was also increased by up to 26% and 110% of the control. AOX, regulated by PPAR-alpha, also increased to 149% and 120% of the control | ||
| 520 | |a CONCLUSION: Reduced expression of PPAR-alpha and AOX was observed even before definite steatosis had developed. The alteration of peroxisomal fatty acid metabolism may have an important role in the development of NAFLD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Fatty Acids |2 NLM | |
| 650 | 7 | |a PPAR alpha |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Acyl-CoA Oxidase |2 NLM | |
| 650 | 7 | |a EC 1.3.3.6 |2 NLM | |
| 700 | 1 | |a Choi, Kyung Mook |e verfasserin |4 aut | |
| 700 | 1 | |a Baik, Sei Hyun |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kyoung Oh |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Hyoung Joon |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Ki Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Jin Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Jong-Jae |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Jae Seon |e verfasserin |4 aut | |
| 700 | 1 | |a Bak, Young-Tae |e verfasserin |4 aut | |
| 700 | 1 | |a Byun, Kwan Soo |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Chang Hong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of gastroenterology and hepatology |d 1989 |g 19(2004), 7 vom: 01. Juli, Seite 799-804 |w (DE-627)NLM012635235 |x 1440-1746 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2004 |g number:7 |g day:01 |g month:07 |g pages:799-804 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2004 |e 7 |b 01 |c 07 |h 799-804 | ||