Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet

Gaetano Serviddio, Anna M. Giudetti, Francesco Bellanti, Paola Priore, Tiziana Rollo, Rosanna Tamborra, Luisa Siculella, Gianluigi Vendemiale, Emanuele Altomare, Gabriele V. Gnoni

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidationimpairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, duringsteatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-Iactivitydecreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO 2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animalswhen compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitishas been here discussed.

Original languageEnglish
Article numbere24084
JournalPLoS One
Volume6
Issue number9
DOIs
Publication statusPublished - Sep 1 2011

Fingerprint

carnitine palmitoyltransferase
beta oxidation
Carnitine
choline
Nutrition
Transferases
Choline
Methionine
methionine
Rats
Fatty Acids
oxidation
Diet
fatty acids
Oxidation
liver
Liver
rats
Fatty Liver
diet

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet. / Serviddio, Gaetano; Giudetti, Anna M.; Bellanti, Francesco; Priore, Paola; Rollo, Tiziana; Tamborra, Rosanna; Siculella, Luisa; Vendemiale, Gianluigi; Altomare, Emanuele; Gnoni, Gabriele V.

In: PLoS One, Vol. 6, No. 9, e24084, 01.09.2011.

Research output: Contribution to journalArticle

Serviddio, G, Giudetti, AM, Bellanti, F, Priore, P, Rollo, T, Tamborra, R, Siculella, L, Vendemiale, G, Altomare, E & Gnoni, GV 2011, 'Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet', PLoS One, vol. 6, no. 9, e24084. https://doi.org/10.1371/journal.pone.0024084
Serviddio, Gaetano ; Giudetti, Anna M. ; Bellanti, Francesco ; Priore, Paola ; Rollo, Tiziana ; Tamborra, Rosanna ; Siculella, Luisa ; Vendemiale, Gianluigi ; Altomare, Emanuele ; Gnoni, Gabriele V. / Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet. In: PLoS One. 2011 ; Vol. 6, No. 9.
@article{2cef76b8b74b429d8c330558b5bed5fb,
title = "Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet",
abstract = "There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidationimpairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, duringsteatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-Iactivitydecreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO 2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animalswhen compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitishas been here discussed.",
author = "Gaetano Serviddio and Giudetti, {Anna M.} and Francesco Bellanti and Paola Priore and Tiziana Rollo and Rosanna Tamborra and Luisa Siculella and Gianluigi Vendemiale and Emanuele Altomare and Gnoni, {Gabriele V.}",
year = "2011",
month = "9",
day = "1",
doi = "10.1371/journal.pone.0024084",
language = "English",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet

AU - Serviddio, Gaetano

AU - Giudetti, Anna M.

AU - Bellanti, Francesco

AU - Priore, Paola

AU - Rollo, Tiziana

AU - Tamborra, Rosanna

AU - Siculella, Luisa

AU - Vendemiale, Gianluigi

AU - Altomare, Emanuele

AU - Gnoni, Gabriele V.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidationimpairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, duringsteatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-Iactivitydecreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO 2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animalswhen compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitishas been here discussed.

AB - There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidationimpairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, duringsteatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-Iactivitydecreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO 2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animalswhen compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitishas been here discussed.

UR - http://www.scopus.com/inward/record.url?scp=80052356803&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052356803&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0024084

DO - 10.1371/journal.pone.0024084

M3 - Article

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e24084

ER -