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Biochemistry (Moscow)

, Volume 84, Issue 9, pp 1093–1106 | Cite as

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

  • S. A. ApryatinEmail author
  • N. V. Trusov
  • A. Yu. Gorbachev
  • V. A. Naumov
  • A. S. Balakina
  • K. V. Mzhel’skaya
  • I. V. GmoshinskiEmail author
Article
  • 5 Downloads

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.

Keywords

transcriptome liver rats RT-PCR dyslipidemia in vivo model 

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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Notes

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”.

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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Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • S. A. Apryatin
    • 1
    Email author
  • N. V. Trusov
    • 1
  • A. Yu. Gorbachev
    • 1
  • V. A. Naumov
    • 2
  • A. S. Balakina
    • 1
  • K. V. Mzhel’skaya
    • 1
  • I. V. Gmoshinski
    • 1
    Email author
  1. 1.Federal Centre of Nutrition, Biotechnology, and Food SafetyMoscowRussia
  2. 2.Kulakov National Medical Research Center of Obstetrics, Gynecology, and PerinatologyMinistry of Health of the Russian FederationMoscowRussia

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