RGD Reference Report - An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: effect of endurance training. - Rat Genome Database

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An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: effect of endurance training.

Authors: Côté, Isabelle  Ngo Sock, Emilienne Tudor  Lévy, Émile  Lavoie, Jean-Marc 
Citation: Côté I, etal., Eur J Nutr. 2013 Aug;52(5):1523-32. doi: 10.1007/s00394-012-0459-5. Epub 2012 Nov 2.
RGD ID: 15045604
Pubmed: PMID:23117815   (View Abstract at PubMed)
DOI: DOI:10.1007/s00394-012-0459-5   (Journal Full-text)


PURPOSE: The aim of this study was to determine the effects of an atherogenic diet (AD; 40 % lipid, 1.25 % cholesterol, kcal) on triglyceride (TAG) and cholesterol accumulation in liver and on gene expression of liver X receptor (LXR) and farnesoid X receptor (FXR) and their target genes and to observe if these responses are affected by endurance training.
METHODS: Sprague-Dawley rats (n = 32) were divided into two groups and randomly assigned to an AD or a standard diet (SD) for 7 weeks. Half of the rats in each group were assigned to an exercise training program for 5 days/week.
RESULTS: The AD resulted in a large (P < 0.01) accumulation in liver TAG (4×) along with elevated liver and plasma cholesterol without any gain in peripheral fat mass. The liver TAG and cholesterol accumulations were associated with an important reduction (P < 0.01; 60 %) in FXR, but no change in LXR transcripts. Accompanying the reduction in FXR gene expression, we found an increase (P < 0.001) in SREBP-1c and a decrease (P < 0.01) in MTP mRNAs suggesting an increased lipogenesis and a reduced VLDL production, respectively. The AD was also associated with lower HMG-CoA-r, squalene synthase, and ABCG8 transcripts (P < 0.001). In the intestine, exercise training resulted in higher NPC1L1, ABCG5, and ABCG8 in SD-fed animals, while all these increases were suppressed under the AD feeding.
CONCLUSIONS: It is concluded that dietary cholesterol favors liver TAG and cholesterol accumulations associated with an important reduction in FXR transcripts.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
metabolic dysfunction-associated steatotic liver disease disease_progressionISOAbcg5 (Rattus norvegicus)15045604; 15045604mRNA:increased expression:liver (rat)RGD 
metabolic dysfunction-associated steatotic liver disease disease_progressionISOAbcg8 (Rattus norvegicus)15045604; 15045604mRNA:decreased expression:liver (rat)RGD 
metabolic dysfunction-associated steatotic liver disease disease_progressionIEP 15045604mRNA:increased expression:liver (rat)RGD 
metabolic dysfunction-associated steatotic liver disease disease_progressionIEP 15045604; 15045604; 15045604mRNA:decreased expression:liver (rat)RGD 
metabolic dysfunction-associated steatotic liver disease disease_progressionISOHmgcr (Rattus norvegicus)15045604; 15045604mRNA:decreased expression:liver (rat)RGD 
metabolic dysfunction-associated steatotic liver disease disease_progressionISONr1h4 (Rattus norvegicus)15045604; 15045604mRNA:decreased expression:liver (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Abcg5  (ATP binding cassette subfamily G member 5)
Abcg8  (ATP binding cassette subfamily G member 8)
Hmgcr  (3-hydroxy-3-methylglutaryl-CoA reductase)
Npc1l1  (NPC1 like intracellular cholesterol transporter 1)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Mus musculus)
Abcg5  (ATP binding cassette subfamily G member 5)
Abcg8  (ATP binding cassette subfamily G member 8)
Hmgcr  (3-hydroxy-3-methylglutaryl-Coenzyme A reductase)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Homo sapiens)
ABCG5  (ATP binding cassette subfamily G member 5)
ABCG8  (ATP binding cassette subfamily G member 8)
HMGCR  (3-hydroxy-3-methylglutaryl-CoA reductase)
NR1H4  (nuclear receptor subfamily 1 group H member 4)


Additional Information