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The effect of hypercaloric diet and Quercetin on the full-transcriptome liver tissue profile of Zucker-LEPRfa rats

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Abstract


BACKGROUND: The peptidic hormone leptin (Lep) occupies a central place in the control of energy homeostasis and body weight in mammals. A convenient model for studying the role of impaired Lep reception is the Zucker-LEPRfa rats, which carry a mutation in the homozygote of the LEPR gene. Quercetin (Q; 3.3 ‘, 4’, 5.7-pentahydroxyflavone) is currently being considered as one of the promising biologically active substances, which allows to correct metabolic disorders in obesity and metabolic syndrome.

AIM: to study changes in the expression of genes in liver tissue of rats with impaired receptivity of Lep under the influence of high-fat and high-carbohydrate diet (HFCR) or/and Q supplementation.

MATERIAL AND METHODS: 4 groups of six male Zucker-LEPRfa male rats were used in experiment. Within 61 days the animals of the 1st group (control) received a balanced semi-synthetic diet, the second group received the same diet with the addition of quercetin in a dose of 50 mg/kg of body weight, the third group — the HFCR (30% fat by dry weight and 20% fructose instead of water), the 4th group is the same diet and supplement of quercetin. Full transcriptional profiling of liver tissue was performed on microchips from the Gene Expression Hybridization Kit (Agilent Technologies), a real-time polymerase chain reaction combined with reverse transcription (RT-PCR) was performed for liver transcripts of Crot, FTO, NpY, Prdx1, Prom1, Ugt2b37 and GAPDH genes contained in liver tissue.

RESULTSIt was shown that feeding of Zucker-LEPRfa rats with Q and/or HFCR led to significant changes in the level of transcription of 1604 genes in liver tissue, from which the effect of quercetin proper was manifested for 1396 genes. Changes were more pronounced in the transcriptome of liver tissue caused by HFCR, than caused by the addition of Q against the background of a standard diet. Q influenced the expression of genes responsible for xenobiotic detoxification processes (UGT2b37), redox homeostasis (Prdx1), beta-oxidation of fatty acids (Crot), and central mechanisms affecting hunger and satiety (NpY), and potentiated, or abolished the effects of HFCR against a number of other functionally important genes. Bioinformatic analysis revealed the influence of HFCR and/or Q on 23 metabolic pathways (KEGGS), of which 7 (the metabolism of steroids, arachidonic and linoleic acids, retinoids, drugs and xenobiotics (due to cytochrome P-450), bile secretion) were affected in all experimental groups.

CONCLUSIONS: Changes in the transcriptome of the liver of Zucker-LEPRfa rats, caused by consumption of HFCR and/or Q, were consistent with experimental data on changes in short-term memory, anxiety and mineral metabolism in these animals.


Nikita V. Trusov

Federal Centre of Nutrition, Biotechnology and Food Safety

Email: nikkitosu@yandex.ru
ORCID iD: 0000-0002-1919-9297
SPIN-code: 5182-2665

Russian Federation, 2/14, Ustinskiy proezd, Moscow, 109240

senior researcher laboratory of food enzymology 

Sergey A. Apryatin

Federal Centre of Nutrition, Biotechnology and Food Safety

Email: apryatin@mail.ru
ORCID iD: 0000-0002-6543-7495
SPIN-code: 4250-2758

Russian Federation, 2/14, Ustinskiy proezd, Moscow, 109240

PhD

Aleksey Yu. Gorbachev

Federal Centre of Nutrition, Biotechnology and Food Safety

Email: augorbachev@gmail.com
ORCID iD: 0000-0002-2743-5835
SPIN-code: 3630-9218

Russian Federation, 2/14, Ustinskiy proezd, Moscow, 109240

PhD

Vladimir A. Naumov

National Medical Research Center of Obstetrics, Gynecology and Perinatology

Email: looongdog@gmail.com
SPIN-code: 9218-7997

Russian Federation, 4, akademika Oparina street, Moscow, 117997

researcher

Kristina V. Mzhelskaya

Federal Centre of Nutrition, Biotechnology and Food Safety

Email: kristik13@yandex.ru
ORCID iD: 0000-0002-0723-5860
SPIN-code: 8608-1400

Russian Federation, 2/14, Ustinskiy proezd, Moscow, 109240

postgraduate laboratory of food enzymology 

Ivan V. Gmoshinski

Federal Centre of Nutrition, Biotechnology and Food Safety

Author for correspondence.
Email: gmosh@ion.ru
ORCID iD: 0000-0002-3671-6508
SPIN-code: 4501-9387
http://www.ion.ru

Russian Federation, 2/14, Ustinskiy proezd, Moscow, 109240

PhD

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Supplementary files

Supplementary Files Action
1. Fig. 1. Venn diagrams. View (153KB) Indexing metadata
2. Fig. 2. Scatter charts “Volcano plots” of differential gene expression in groups of animals 2 (a), 3 (b) and 4 (c) in comparison with the 1st group. View (751KB) Indexing metadata
3. Fig. 3. Venn diagram of distribution of Zucker-LEPRfa rats of metabolic pathways, which are the targets of the dietary effects used. View (70KB) Indexing metadata
4. Fig. 4. Comparative changes in the metabolic pathway of STEROID HORMONE BIOSYNTHESIS in rats Zucker-LEPRfa group 2 (a), in comparison with the 1st group. View (770KB) Indexing metadata
5. Fig. 4. Comparative changes in the metabolic pathway of STEROID HORMONE BIOSYNTHESIS in Zucker-LEPRfa group 3 (b) rats in comparison with the 1st group. View (769KB) Indexing metadata
6. Fig. 4. Comparative changes in the metabolic pathway of STEROID HORMONE BIOSYNTHESIS in Zucker-LEPRfa rats of groups 2 (a), 3 (b) and 4 (c) in comparison with the 1st group. View (763KB) Indexing metadata
7. Fig. 5. Levels of total calcium and phosphorus in the blood plasma of rats Zucker-LEPRfa 1-4 groups when removed from the experiment. View (81KB) Indexing metadata
8. Fig. 6. Changes in the expression of the Сrot, FTO, NpY, Prdx1, Prom1, Ugt2b37, GAPDH genes in the liver of Zucker-LEPRfa rats according to RT PCR data. View (348KB) Indexing metadata

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Copyright (c) 2019 Trusov N.V., Apryatin S.A., Gorbachev A.Y., Naumov V.A., Mzhelskaya K.V., Gmoshinski I.V.

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