PMID- 22340678
OWN - NLM
STAT- MEDLINE
DCOM- 20121010
LR  - 20161125
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Linking)
VI  - 32
IP  - 6
DP  - 2012 Jul
TI  - Identification of liver proteins altered by type 2 diabetes mellitus in obese 
      subjects.
PG  - 951-61
LID - 10.1111/j.1478-3231.2012.02765.x [doi]
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a well-known factor risk for 
      non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis 
      (NASH) in obese patients. AIMS: To better understand the association between T2DM 
      and NAFLD, global changes in protein expression in diabetic and non-diabetic 
      obese subjects were assessed by a proteomic approach. METHODS: Liver samples were 
      obtained from diabetic and non-diabetic morbid obese subjects (BMI>40 kg/m(2) ). 
      Histological analysis was used to evaluate hepatic steatosis and the degree of 
      anatomopathological alteration. Changes in protein expression were analysed by 
      two-dimentional electrophoresis combined with MALDI-TOF mass spectrometry. Levels 
      of glutathione, carbonyl and 4-HNE protein adducts were used to assess oxidative 
      stress status. RESULTS: Of 850 proteins analysed, 33 were differentially 
      expressed in T2DM obese subjects. Of these, 27 were unequivocally identified by 
      mass spectrometry. Analysis of protein sets revealed patterns of decreased 
      abundance in mitochondrial enzymes, proteins involved in methione metabolism, and 
      oxidative stress response. Accordingly, T2DM subjects showed decreased levels of 
      glutathione, the antioxidant byproduct of methionine metabolism via the 
      transsulfuration pathway, and higher levels of protein and lipid oxidative 
      damage. Changes in detoxyfing enzymes, carbohydrate metabolism, proteasome 
      subunits and retinoic acid synthesis were also found. CONCLUSIONS: The results 
      suggest alterations in mitochondrial function and methionine metabolism as 
      potential contributing factors to increased oxidative stress in liver of obese 
      diabetic patients which may be influencing the development of NAFLD and NASH.
CI  - (c) 2012 John Wiley & Sons A/S.
FAU - Valle, Adamo
AU  - Valle A
AD  - Grupo Multidisciplinar de Oncologia Traslacional, Institut Universitari 
      d'Investigacio en Ciencies de la Salut, Universitat de les Illes Balears, Palma 
      de Mallorca, Spain.
FAU - Catalan, Victoria
AU  - Catalan V
FAU - Rodriguez, Amaia
AU  - Rodriguez A
FAU - Rotellar, Fernando
AU  - Rotellar F
FAU - Valenti, Victor
AU  - Valenti V
FAU - Silva, Camilo
AU  - Silva C
FAU - Salvador, Javier
AU  - Salvador J
FAU - Fruhbeck, Gma
AU  - Fruhbeck G
FAU - Gomez-Ambrosi, Javier
AU  - Gomez-Ambrosi J
FAU - Roca, Pilar
AU  - Roca P
FAU - Oliver, Jordi
AU  - Oliver J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120219
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (Aldehydes)
RN  - 0 (Biomarkers)
RN  - 0 (Proteins)
RN  - AE28F7PNPL (Methionine)
RN  - GAN16C9B8O (Glutathione)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
MH  - Adult
MH  - Aldehydes/analysis
MH  - Biomarkers/analysis
MH  - Biopsy
MH  - Diabetes Mellitus, Type 2/*complications/metabolism
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Fatty Liver/*etiology/metabolism/pathology
MH  - Female
MH  - Glutathione/analysis
MH  - Humans
MH  - Liver/*chemistry/pathology
MH  - Methionine/analysis
MH  - Middle Aged
MH  - Mitochondria, Liver/chemistry
MH  - Non-alcoholic Fatty Liver Disease
MH  - Obesity, Morbid/*complications/metabolism
MH  - Oxidative Stress
MH  - Protein Carbonylation
MH  - Proteins/*analysis
MH  - Proteomics/methods
MH  - Severity of Illness Index
MH  - Spain
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
EDAT- 2012/02/22 06:00
MHDA- 2012/10/12 06:00
CRDT- 2012/02/21 06:00
PHST- 2011/10/19 00:00 [received]
PHST- 2012/01/15 00:00 [accepted]
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
AID - 10.1111/j.1478-3231.2012.02765.x [doi]
PST - ppublish
SO  - Liver Int. 2012 Jul;32(6):951-61. doi: 10.1111/j.1478-3231.2012.02765.x. Epub 
      2012 Feb 19.