RGD Reference Report - Ketone body production is differentially altered in steatosis and non-alcoholic steatohepatitis in obese humans. - Rat Genome Database

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Ketone body production is differentially altered in steatosis and non-alcoholic steatohepatitis in obese humans.

Authors: Männistö, Ville T  Simonen, Marko  Hyysalo, Jenni  Soininen, Pasi  Kangas, Antti J  Kaminska, Dorota  Matte, Ananda K  Venesmaa, Sari  Käkelä, Pirjo  Kärjä, Vesa  Arola, Johanna  Gylling, Helena  Cederberg, Henna  Kuusisto, Johanna  Laakso, Markku  Yki-Järvinen, Hannele  Ala-Korpela, Mika  Pihlajamäki, Jussi 
Citation: Männistö VT, etal., Liver Int. 2015 Jul;35(7):1853-61. doi: 10.1111/liv.12769. Epub 2015 Jan 20.
RGD ID: 13831308
Pubmed: PMID:25533197   (View Abstract at PubMed)
DOI: DOI:10.1111/liv.12769   (Journal Full-text)


BACKGROUND & AIMS: Levels of ketone bodies have been reported to be both increased and decreased in individuals with non-alcoholic fatty liver disease. We investigated whether the metabolism of ketone bodies is different in simple steatosis and in non-alcoholic steatohepatitis (NASH).
METHODS: Serum low molecular weight molecules including ketone bodies were measured using high-throughput proton (1H) nuclear magnetic resonance in 116 (76 categorized unequivocally to those with normal liver, simple steatosis or NASH) morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, body mass index 45.1 ± 6.1 kg/m(2) , 39 men and 77 women] with histological assessment of NASH and analysis of gene expression in the liver. Finally, we correlated β-hydroxybutyrate (β-OHB) levels with NASH predicting score in Metabolic Syndrome in Men Study (METSIM) population study (n = 8749 non-diabetic men).
RESULTS: Levels of ketone bodies were lower in individuals with NASH compared to individuals with simple steatosis (P = 0.004 and P = 0.018 for β-OHB and acetoacetate respectively). Lower levels of β-OHB were associated with the NASH predicting score in the METSIM study (P = 0.001). Liver inflammation correlated with mRNA expression of genes regulating ketolysis in the liver (Spearman correlation 0.379-0.388, P < 0.0006 for ACAT1, ACSS2 and BDH1).
CONCLUSION: Lower levels of ketone bodies in individuals with NASH compared to individuals with simple steatosis suggest a decrease in ketone body metabolism in NASH.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Inflammation  IEP 13831308associated with nonalcoholic fatty liver diseaseRGD 
Inflammation  ISOACSS2 (Homo sapiens)13831308; 13831308associated with nonalcoholic fatty liver diseaseRGD 

Objects Annotated

Genes (Rattus norvegicus)
Acss2  (acyl-CoA synthetase short-chain family member 2)

Genes (Mus musculus)
Acss2  (acyl-CoA synthetase short-chain family member 2)

Genes (Homo sapiens)
ACSS2  (acyl-CoA synthetase short chain family member 2)


Additional Information