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Comparative Whole-Transcriptome Profiling of Liver Tissue from Wistar Rats Fed with Diets Containing Different Amounts of Fat, Fructose, and Cholesterol

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Abstract

Differential expression of 30,003 genes was studied in the liver of female Wistar rats fed with isocaloric diets with the excess of fat, fructose, or cholesterol, or their combinations for 62 days using the method of whole-transcriptome pro-filing on a microchip. Relative mRNA expression levels of the Asah2, Crot, Crtc2, Fmo3, GSTA2, LOC1009122026, LOC102551184, NpY, NqO1, Prom1, Retsat, RGD1305464, Tmem104, and Whsc1 genes were also determined by RT-qPCR. All the tested diets affected differently the key metabolic pathways (KEGGs). Significant changes in the expression of steroid metabolism gene were observed in the liver of animals fed with the tested diets (except the high-fat high fructose diet). Both high-fat and high-fructose diets caused a significant decrease in the expression of squalene synthase (FDFT1 gene) responsible for the initial stage of cholesterol synthesis. On the contrary, in animals fed with the high-cholesterol diet (0.5% cholesterol), expression of the FDFT1 gene did not differ from the control group; however, these animals were characterized by changes in the expression of glucose and glycogen synthesis genes, which could lead to the suppression of glycogen synthesis and gluconeogenesis. At the same time, this group demonstrated different liver tissue morphology in comparison with the animals fed with the high-fructose high-fat diet, manifested as the presence of lipid vacuoles of a smaller size in hepatocytes. The high-fructose and high-fructose high-fat diets affected the metabolic pathways associated with intracellular protein catabolism (endocytosis, phagocytosis, proteasomal degradation, protein processing in the endoplasmic reticulum), tight junctions and intercellular contacts, adhesion molecules, and intracellular RNA transport. Rats fed with the high-fructose high-fat or high-cholesterol diets demonstrated consistent changes in the expression of the Crot, Prom1, and RGD1305464 genes, which reflected a coordinated shift in the regulation of lipid and carbohydrate metabolisms.

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Abbreviations

AIN93M:

93M diet of the American Institute of Nutrition

Asah2 :

N-acylsphingosine amidohydrolase 2 gene (ceramidase)

Crot :

carnitine octanoyltransferase gene

Crtc2 :

CREB-regulated transcription coactivator 2

FAM:

carboxyfluorescein

FDFT1 :

farnesyl-diphosphate farnesyltransferase 1 (squalene synthase) gene

Fmo3 :

flavin-containing monooxygenase 3 gene

GSTA2 :

glutathione-S-transferase alpha 2 gene

HCD:

high-cholesterol diet

HCHFrD:

high-cholesterol high-fructose diet

HFaD:

high-fat diet

HFaHFrD:

high-fat high-fructose diet

HFrD:

high-fructose diet

Inhbb :

inhibin beta B chain (activin β-subunit) gene

LOC1009122026 :

1009122026 gene

LOC102551184 :

102551184 gene

MS:

metabolic syndrome

NpY :

neuropeptide Y gene

NqO1 :

NAD(P)H dehydrogenase, (quinone 1) gene

Prom1 :

prominin 1 gene

Retsat :

retinol saturase gene

RGD1305464 (Sept14):

GTP-binding cytoskeletal protein 1305464 or SEPT14 gene

RT-qPCR:

reverse transcription/quantitative polymerase chain reaction

SSD:

semisynthetic diet

TGF-β:

tumor growth factor beta

Tmem104 :

transmembrane protein 104 gene

Ugt2b37 :

uridine diphosphate glycosyltransferase 2 family, member b17 gene

Whsc1 :

Wolf-Hirschhorn syndrome candidate 1 gene

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Funding

Funding. This study was supported by the State Budget Project of the Ministry of Education and Science of Russia no. 0529-2015-0006 “Search for New Molecular Markers of Alimentary Diseases: Genomic and Post-genomic Analysis”.

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Authors and Affiliations

  1. Federal Centre of Nutrition, Biotechnology, and Food Safety, 109240, Moscow, Russia

    S. A. Apryatin, N. V. Trusov, A. Yu. Gorbachev, A. S. Balakina, K. V. Mzhel’skaya & I. V. Gmoshinski

  2. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, 117198, Moscow, Russia

    V. A. Naumov

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  1. S. A. Apryatin
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  2. N. V. Trusov
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  3. A. Yu. Gorbachev
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  5. A. S. Balakina
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  6. K. V. Mzhel’skaya
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Correspondence to S. A. Apryatin or I. V. Gmoshinski.

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Ethical approval. All applicable international, national, and/or institutional guidelines for the care and use of laboratory animals were followed in this study.

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Conflict of interest. The authors declare no conflict of interest in financial or any other sphere.

Russian Text © The Author(s), 2019, published in Biokhimiya, 2019, Vol. 84, No. 9, pp. 1344–1358.

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Apryatin, S.A., Trusov, N.V., Gorbachev, A.Y. et al. Comparative Whole-Transcriptome Profiling of Liver Tissue from Wistar Rats Fed with Diets Containing Different Amounts of Fat, Fructose, and Cholesterol. Biochemistry Moscow 84, 1093–1106 (2019). https://doi.org/10.1134/S0006297919090128

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