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

2019 ◽  
Vol 64 (6) ◽  
pp. 371-382
Author(s):  
Nikita V. Trusov ◽  
Sergey A. Apryatin ◽  
Aleksey Yu. Gorbachev ◽  
Vladimir A. Naumov ◽  
Kristina V. Mzhelskaya ◽  
...  

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. RESULTS: It 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.

2018 ◽  
Vol 20 (88) ◽  
pp. 29-35
Author(s):  
M. Zhyla ◽  
M. Shkil ◽  
Y. Stronskyi

In the article presents the results of the pathomorphological study on the toxicity of the new veterinary preparation immunomodulatory “Bioton”, to solution for per oral application that contains complex biologically active foods of metabolism of mushrooms-entophytes (Cylindrocarpon Magnusianum), medical plants abstracted from a root. The study of subacute toxicity of the preparation “Bioton” was carried out on male rats, with a body weight of 170–180 g, formed in two groups of 30 rats in each: I group (control) – received water; The second group was given an oral preparation “Bioton” at a rate of 170 mg/kg of body weight of the rat. Animals were kept under the conditions of vivarium SSRCIVMPFD of veterinary preparations and food supplements, with constant temperature of premises and humidity. The feeding provided a standard diet with constant access to water. The experimental studies carried out have found that intrauterine injection of “Bioton” drugs in a dose of 170 mg/kg of body weight for 30 days caused stimulation of immune protection factors, which was shown by a significant increase in the content of T- and B-lymphocytes and NK-cells, did not cause macro- and microscopic changes in the internal organs, and an increase in the coefficients of the mass of the thymus, spleen and testicles indicated the functional activity of organs with a high proliferative capacity of the parenchymal elements. Then, as the application for 60 days, caused negative changes in the morphological and immunological parameters of the blood, namely reduction of the number of red blood cells, hemoglobin content and growth of leukocytes due to the increase of neutrophil granulocytes, against the background of reduction of T- and B-lymphocytes, NK-cells compared to the control groups and development of pathological processes in the internal organs of rats. Histologically, the presence of the occidental involution of thymus and the cellular devastation of parenchyma of peripheral organs of the immune system of rats receiving the Bioton preparation for 60 days were confirmed. In further work an analysis of the biochemical parameters of blood of rats obtained for the study of toxicity of the drug “Bioton” will be conducted.


2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.


1958 ◽  
Vol 4 (6) ◽  
pp. 771-776 ◽  
Author(s):  
Mary L. Petermann ◽  
Mary G. Hamilton

Rat liver was homogenized in 0.88 M sucrose. The DNA and total RNA were determined, and the homogenate was fractionated by differential centrifugation. The pellets obtained between 30 minutes at 20,000 g and 180 minutes at 105,000 g were analyzed for RNA and nitrogen. The ribonucleoproteins were determined in the analytical ultracentrifuge. The non-pellet RNA was calculated by difference. The results are reported as amounts per 6.7 x 10-9 mg. of DNA. In young, growing male rats the amounts of microsomal protein and ribonucleoprotein B (83S) increased with age. Non-pregnant adult females showed less non-pellet RNA and much more ribonucleoprotein C (63S) than did adult males. During pregnancy both of these cell constituents reverted to levels characteristic for male animals. Starvation for 5 days resulted in a reduction in the mass of liver tissue, the non-pellet RNA, the microsomal protein, and ribonucleoproteins B and C. During recovery from starvation the return of the liver to normal paralleled the rate at which body weight was restored. Treatment with cortisone, 25 mg. per rat per day for 5 days, caused an increase in microsomal protein and a decrease in ribonucleoprotein B. Treatment with 6-mercapto-purine, 50 mg. per kilo per day for 5 days, caused little change in liver composition in either males or females.


2000 ◽  
pp. 406-410 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
J Navarro ◽  
C Dieguez ◽  
...  

The obese gene (ob) product, leptin, has recently emerged as a key element in body weight homeostasis, neuroendocrine function and fertility. Identification of biologically active, readily synthesized fragments of the leptin molecule has drawn considerable attention, as they may provide a powerful tool for detailed characterization of the biological actions of leptin in different experimental settings. Recently, a fragment of mouse leptin protein comprising amino acids 116-130, termed leptin(116-130) amide, was shown to mimic the effects of the native molecule in terms of body weight gain and food intake, and to elicit LH and prolactin (PRL) secretion in vivo. As a continuation of our previous experimental work, the present study reports on the effects of leptin(116-130) amide on basal and stimulated testosterone secretion by adult rat testis in vitro. In addition, a comparison of the effects of human recombinant leptin and leptin(116-130) amide at the pituitary level on the patterns of LH, FSH, PRL and GH secretion is presented. As reported previously by our group, human recombinant leptin(10(-9)-10(-7)M) significantly inhibited both basal and human chorionic gonadotrophin (hCG)-stimulated testosterone secretion in vitro. Similarly, incubation of testicular tissue in the presence of increasing concentrations of leptin(116-130) amide (10(-9)-10(-5)M) resulted in a dose-dependent inhibition of basal and hCG-stimulated testosterone secretion; a reduction that was significant from a dose of 10(-7)M upwards. In addition, leptin(116-130) amide, at all doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secretion by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin(10(-9)-10(-7)M) was ineffective in modulating LH and FSH release. Finally, neither recombinant leptin nor leptin(116-130) amide were able to change basal PRL and GH secretion in vitro. Our results confirm the ability of leptin, acting at the testicular level, to inhibit testosterone secretion, and map the effect to a domain of the leptin molecule that lies between amino acid residues 116 and 130. In addition, we provide evidence for a direct inhibitory action of leptin(116-130) amide on pituitary LH and FSH secretion, a phenomenon not observed for the native leptin molecule, in the adult male rat.


2008 ◽  
Vol 100 (6) ◽  
pp. 1192-1199 ◽  
Author(s):  
Pascale Rozan ◽  
Amine Nejdi ◽  
Sophie Hidalgo ◽  
Jean-François Bisson ◽  
Didier Desor ◽  
...  

Ageing is associated with changes in physiology and morphology; nutritional strategies to decrease morbidity and to prolong life are of high interest. The aim of the study was to investigate the effects of lifelong supplementation with an oligofructose-enriched inulin on morphological and biological markers and lifespan in male and female rats. Male and female rats, age 3 months, were randomised into two groups to receive either a diet with 10 % of an oligofructose-enriched inulin (Synergy1) or a standard diet (control) for 27 months. The rats were weighed every 2 weeks and their food intake was evaluated on four successive days every 4–6 weeks. Samples were taken at 12, 18 and 24 months of age. During the whole intervention period, male rats receiving Synergy1 (SYN1-M) displayed lower body weight, cholesterol and plasma triacylglycerolaemia compared with the controls (Cont-M). The survival rate at 24 months of age of SYN1-M rats was 35·3 % greater than that of Cont-M rats. In female rats, the Synergy1 supplementation (SYN1-F) group also reduced body weight, cholesterol and triacylglycerolaemia levels, but results were less consistent over the experiment. The survival rate at 24 months of age in SYN1-F rats was 33·3 % greater compared with that of the control (Cont-F) group. To conclude, lifelong intervention with Synergy1 improved biological markers during ageing and survival rate (lifespan) of rats.


Author(s):  
N. H. Kopchak ◽  
О. S. Pokotylo ◽  
M. D. Kuhtyn ◽  
M. I. Koval

Introduction. Today, obesity is an extremely common phenomenon that negatively affects on the functional state of the organism, metabolism, and this in turn leads to the increase of a number of diseases. The thyroid gland has a significant effect on lipid metabolism, and especially negative in the case of iodine deficiency in the diet, which leads to hypothyroidism. Comparative study of the effect of various iodine-derived lipid metabolism in obesity is perspective.The aim of the study – to investigate the comparative affect of biologically active iodine in the composition of “Jodis-Concentrate” and inorganic iodine (J-C) as a part of “Iodomarine” on the indicators of lipid metabolism in blood of white male rats with experimental alimentary obesity.Research Methods. The object of the study was the blood serum of white rats, and the subject – separate indicators of lipid metabolism in it. The study was conducted on 48 white male rats. Animals were divided into 3 age groups of 16 animals in each: 1st group – 1.5 months; 2nd – 2.5 months; 3rd – 5th month. In each age group there were 4 subgroups of 4 animals: 1st – control, had a typical diet; 2nd, 3rd and 4th subgroup were with experimental alimentary obesity (EAO), which was formed through the inductor food craving – the sodium salt of glutamic acid in a ratio of 0.6 : 100.0 and high-calorie diet that included standard meals (47 %), sweet condensed milk (44 %), corn oil (8 %) and vegetable starch (1 %). Daily for 45 days, animals of the 3rd subgroup received biologically active iodine in the composition of “Jodis-Concentrate” (J-C) as of 0.1 ml (0.4 mcg of iodine) per kg of body weight a day and 4th subgroup were intragastric administered in the form of inorganic iodine as potassium iodide in medicine “Iodomarin” (IM) as of 0.4 mcg of potassium iodide per kg of body weight a day. In the serum blood, the content of total lipids, total cholesterol, triglycerides, high and low density lipoprotein were determined.Results and Discussion. The obtained results suggest that with the help of biologically active iodine in the composition of “Jodis-Concentrate” there was a significant decrease of the content of common lipids, triglycerides, total cholesterol, low density lipoprotein in blood serum of males with different age than with “Iodomarin”.Conclusions. Given the effective results of the study of the hypolipidemic effect of J-C it is advisable to use it as a preventive and therapeutic agent for reducing the content of common lipids of triglycerides, total cholesterol, and low density lipoproteins in the blood.


Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2000
Author(s):  
Laura Menchetti ◽  
Giulio Curone ◽  
Egon Andoni ◽  
Olimpia Barbato ◽  
Alessandro Troisi ◽  
...  

This study examined the effects of goji berries dietary supplementation on the energetic metabolism of doe. Thirty days before artificial insemination, 75 New Zealand White does were assigned to three different diets: commercial standard diet (C) and supplemented with 1% (LG) and 3% (HG) of goji berries, respectively. Body conditions, hormones and metabolites were monitored until weaning. Body weight and BCS were higher in HG than C (p < 0.05). LG showed lower T3/T4 ratio and cortisol concentrations (p < 0.05) and tended to have lower indices of insulin resistances (p < 0.1) than HG. Compared to control, leptin was higher in HG at AI (p < 0.01) and in LG during lactation (p < 0.05). Two principal components were extracted by multivariate analysis describing the relationships between (1) non-esterified fatty acids, insulin and glucose levels, and (2) body conditions and leptin metabolism. The first component highlighted the energy deficit and the insulin resistance of the does during pregnancy and lactation. The second one showed that leptin, body weight and Body Condition Score (BCS) enhance as levels of goji berries in the diet increase. Thus, the effects of goji supplementation are dose-dependent: an improvement on energy metabolism was achieved with a low-dose while the highest dose could determine excessive fattening and insulin resistance in does.


2020 ◽  
Vol 22 (99) ◽  
pp. 24-28
Author(s):  
T. M. Kaliuzhna ◽  
H. A. Fotina

Modern veterinary medicine has made great strides in the prevention and treatment of various diseases, largely through the availability of highly effective drugs. One of the major challenges to development of effective, safe, competitive drugs in Ukraine is the creation of an effective system of pre-clinical trials that meet international standards. The toxicity study is a mandatory phase trials of new drugs. The drug “Inkombivit” accommodates only available endogenous biologically active substances, which are natural feed ingredients for animals and are naturally present in animal tissues. All active pharmaceutical ingredients used in drug “Inkombivit”, by the EU regulation No. 37/2010 related to non-hazardous for animals and people compounds. The LD50 of most active pharmaceutical ingredients included in the drug “Incombivit” for mice when administered orally ranges from 5000 to 10000 mg/kg body weight, except for some active pharmaceutical ingredients when they are contained in milligram amounts in 1 liter of the drug, for which LD50 less than 1000 mg/kg body weight of animals. Incombivit is a combination drug that contains fat- and water-soluble vitamins, trace elements and amino acids that normalize metabolism, increase overall resistance, improve productivity, safety and reproductive functions of animals. Acute toxicity of the drug was studied on 50 white mice weighing 19–21 g and on 20 white rats weighing 250–295 g. The animals were kept in accordance with sanitary norms and rules on a standard diet (compound feed) adopted in the vivarium. The acute LD50 of Incombivit for a single oral administration is 7500 ± 229.95 mg/kg body weight for mice and 6250 ± 375.50 mg/kg body weight for rats. Incombivit can be classified as hazard class 4 according to the International Standard GOST 12.1.007-76 and to category 5 according to the International Global Harmonized System (GHS) classification, as its LD50 for mice and rats with a single oral administration exceeds 5000 mg/kg body weight.


2008 ◽  
Vol 294 (2) ◽  
pp. R290-R301 ◽  
Author(s):  
Christa M. Patterson ◽  
Ambrose A. Dunn-Meynell ◽  
Barry E. Levin

We assessed the effect of early-onset exercise as a means of preventing childhood obesity using juvenile male rats selectively bred to develop diet-induced obesity (DIO) or to be diet resistant (DR) when fed a 31% fat high-energy diet. Voluntary wheel running begun at 36 days of age selectively reduced adiposity in DIO vs. DR rats. Other 4-wk-old DIO rats fed a high-energy diet and exercised (Ex) for 13 wk increased their core temperature, gained 22% less body weight, and had 39% lighter fat pads compared with sedentary (Sed) rats. When wheels were removed after 6 wk (6 wk Ex/7 wk Sed), rats gained less body weight over the next 7 wk than Sed rats and still had comparable adipose pad weights to 13-wk-exercised rats. In fact, only 3 wk of exercise sufficed to prevent obesity for 10 wk after wheel removal. Terminally, the 6-wk-Ex/7-wk-Sed rats had a 55% increase in arcuate nucleus proopiomelanocortin mRNA expression vs. Sed rats, suggesting that this contributed to their sustained obesity resistance. Finally, when Sed rats were calorically restricted for 6 wk to weight match them to Ex rats (6 wk Rstr/7 wk Al), they increased their intake and body weight when fed ad libitum and, after 7 wk more, had higher leptin levels and adiposity than Sed rats. Thus, early-onset exercise may favorably alter, while early caloric restriction may unfavorably influence, the development of the hypothalamic pathways controlling energy homeostasis during brain development.


2019 ◽  
Vol 25 (1) ◽  
pp. 32-38
Author(s):  
K.V. Pivtorak

The improvement of the pharmacological strategy of non-alcoholic fatty liver disease is based on the study of the effect of pharmaceutical preparations on the structure and function of the liver. The pathogenesis of steatohepatitis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. The purpose of the study was to characterize the structural and functional parameters of the liver when using the biologically active compound Angiolin for the correction of experimental steatohepatitis. An experimental study was performed on 110 sexually mature white male rats weighing 180-220 grams, which were kept on a standard diet of vivarium. All animals were divided into two groups: control (30 intact animals) and experimental (80 animals). A model of non-alcoholic steatohepatitis was created for all animals of the experimental group. They were kept on a hypercaloric diet with a high fat and high cholesterol content for 8 weeks. After that, part of the animals (10 rats) was withdrawn from the experiment by intrapleural administration of sodium thiopental (50 mg/kg) and the necessary biochemical and morphological studies were performed. Part of the animals (30 rats) was continued to be kept on a high-fat diet for 4 weeks and the biologically active compound Angiolin was administered (20 rats), and Rings-Locke solutions were administered to 10 rats. After the creation of the model, the other animals of the experimental group (40 rats) were transferred to a full-fledged standard semi-synthetic starch-casein diet, and the biologically active compound Angiolin was administered for 20 rats and Ringer-Locke solution for another 20 rats for 4 weeks. Macroscopic evaluation and description of the liver of animals was carried out after withdrawal under thiopental anesthesia. Statistical analysis of the results was carried out using the program “STATISTICA 8” using parametric and non-parametric methods for assessing the results. It was found that the use of the biologically active compound Angiolin once a day for 30 days can reduce cytolysis syndrome (reduce biochemical parameters such as ALT, AST, gamma-glutamyl transpeptidase), reduce cholestasis syndrome (decrease in alkaline phosphatase level), and normalize liver function, improves the morphological state of hepatocytes, which indicates the normalization of the structural and functional state of the liver.


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