scholarly journals STUDY OF SPECIFIC ANTIDIABETIC EFFECT OF PERSPECTIVE SIRTUIN-1 ACTIVATOR PYRABENTIN ON THE MODEL OF METABOLIC MEMORY IN RATS

2021 ◽  
Vol 76 (2) ◽  
Author(s):  
N.S. Krasova ◽  
Alexandr Gladkih ◽  
Fedir Yaremenko ◽  
Zhanna Leshchenko ◽  
Alla Kolesnikova ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Sirtuin 1 ◽  
Comparable Efficacy ◽  
Metabolic Memory ◽  
Standard Diet ◽  
Reference Drug ◽  
Abdominal Adipose Tissue ◽  
Antidiabetic Effect

Pharmacological activation of sirtuin-1 (SIRT1), which can mimic calorie restriction, reduce fat deposition along with stimulating its utilization, and possibly erase "metabolic memory", is a promising goal for the prevention and treatment of obesity and type 2 diabetes. The aim of the study was to evaluate the specific antidiabetic effect of the original heterocyclic compound with the proprietary name pyrabentin with in situ proven ability to activate human sirtuin-1 on the experimental model of "metabolic memory" in rats. The study was conducted on adult male Wistar rats (n=24), which were kept on a high-fat diet (HFD) for 5 months, control sex- and age-matched animals (n=6) were received standard diet (StD). At the end of the 5-mo HFD-period, the animals were randomized for the study over the next two months into 4 groups as follows: HFD/HFD+placebo, HFD/StD+placebo, HFD/StD+pyrabentin (PB), HFD/StD+metformin (MF). PB was administered orally at 50 mg/kg body weight as an aqueous suspension with Tween-80 daily, the reference drug metformin was administered in a similar way at 100 mg/kg body weight, the control group received a placebo. Glucose tolerance test and short insulin test were performed, body weight, abdominal adipose tissue weight by fraction and blood pressure were assessed. Shapiro-Wilk test, paired and unpaired Student’s t-test, and Mann-Whitney U-test were used. It was found that 60-day administration of pyrabentin to rats with a model of "metabolic memory", insulin resistance and obesity, was realized in a statistically significant decrease in basal glycemia, glucose intolerance, body weight and weight of abdominal adipose tissue fractions with comparable efficacy to the reference drug. This was accompanied by improved insulin sensitivity and blood pressure.

EFFECTS OF PERSPECTIVE SIRTUIN-1 ACTIVATOR ON ENERGY HOMEOSTASIS CONSTITUENTS IN RATS WITH E XPERIMENTAL T YPE 2 DIABETES MELLITUS AT THE BACKGROUND OF OBESITY

2019 ◽  
Vol 70 (4) ◽  
pp. 116-122
Author(s):  
Nataliya Krasova ◽  
A. I. Gladkih ◽  
Fedir Yaremenko ◽  
T. V. Tyzhnenko ◽  
Zhanna Leshchenko ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Oxidative Phosphorylation ◽  
Energy Homeostasis ◽  
Relative Weight ◽  
Sirtuin 1 ◽  
Comparable Efficacy ◽  
Control Group ◽  
Reference Drug ◽  
Abdominal Adipose Tissue

NAD+-dependent deacetylase, sirtuin-1 (SIRT1), is a promising pharmacological target for the treatment ofage-related disorders, including obesity and type 2 diabetes mellitus (DM2). The aim of the work was to evaluate the effect of the original heterocyclic compound with the proprietary name pyrabentin with in situ provenability to activate human sirtuin-1 on the energy homeostasis components in rats with experimental DM2 andobesity. The study was conducted on adult male Wistar rats (n = 24). DM2 with obesity was induced by lowdose of streptozotocin after 100-day’s combined high-fat and high-fructose diet consumption; control sex- andage-matched animals were received standard nutrition. Pyrabentin was administered orally at 50 mg/kg bodyweight as an aqueous suspension with Tween-80 daily for 30 days. The reference drug metformin was administered in a similar way at 50 mg/kg body weight, the control group received a placebo. Glucose tolerance by theglucose oxidase method, enzyme lipid profile, abdominal adipose tissue mass by fractions, and the functionalstate of hepatocyte mitochondria by respiration intensity and oxidative phosphorylation by the polarographicmethod were evaluated. It was established that the 30-day administration of pyrabentine to rats with DM2 wasrealized in a statistically significant decrease in basal glycemia, glucose intolerance, dyslipidemia, body weightand relative weight of abdominal adipose tissue fractions with comparable efficacy to the reference drug. Thiswas accompanied by an improvement in oxidative phosphorylation and, accordingly, in the functional activity ofliver mitochondria.

Mechanisms contributing to angiotensin II regulation of body weight

1998 ◽  
Vol 274 (5) ◽  
pp. E867-E876 ◽  
Author(s):  
Lisa A. Cassis ◽  
Dana E. Marshall ◽  
Michael J. Fettinger ◽  
Brady Rosenbluth ◽  
Robert A. Lodder
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Infrared Imaging ◽  
Ang Ii ◽  
Tissue Mass ◽  
Thermal Infrared Imaging ◽  
Weight Decrease ◽  
The Impact

Previous studies in our laboratory have implicated adipose tissue as a potential site for local angiotensin II (ANG II) synthesis. However, functions of ANG II in adipose tissue and the impact of ANG II on body weight regulation are not well defined. To study the effect of ANG II on body weight, a chronic ANG II infusion model was used. In study 1, a low dose of ANG II (175 ng ⋅ kg−1 ⋅ min−1) was infused into rats for 14 days. Plasma ANG II levels were not elevated after 14 days of infusion. ANG II-infused rats did not gain weight over the 14-day protocol and exhibited a lower body weight than controls on day 8. Food intake was not altered, but water intake was increased in ANG II-infused rats. Blood pressure gradually increased to significantly elevated levels by day 14. Thermal infrared imaging demonstrated an increase in abdominal surface temperature. Measurement of organ mass demonstrated site-specific reductions in white adipose tissue mass after ANG II infusion. In study 2, the dose-response relationship for ANG II infusion (200, 350, and 500 ng ⋅ kg−1 ⋅ min−1) was determined. Body weight (decrease), blood pressure (increase), white adipose mass (decrease), plasma ANG II levels (increase), and plasma leptin levels (decrease) were altered in a dose-related manner after ANG II infusion. In study 3, the effect of ANG II infusion (350 ng ⋅ kg−1 ⋅ min−1) was examined in rats treated with the vasodilator hydralazine. Hydralazine treatment normalized blood pressure in ANG II-infused rats. The effect of ANG II to decrease body weight was augmented in hydralazine-treated rats. These results demonstrate that low levels of ANG II infusion regulate body weight through mechanisms related to increased peripheral metabolism and independent of elevations in blood pressure.

Changes in Abdominal Adipose Tissue Compartments with Changes in Body Weight

2007 ◽  
Vol 39 (Supplement) ◽  
pp. 68
Author(s):  
Shana O. Warner ◽  
R. Scott Rector ◽  
Ying Liu ◽  
Pamela S. Hinton ◽  
David R. Huyette ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Abdominal Adipose Tissue ◽  
Tissue Compartments

Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers

2005 ◽  
Vol 288 (6) ◽  
pp. E1236-E1243 ◽  
Author(s):  
Elena Velkoska ◽  
Timothy J. Cole ◽  
Margaret J. Morris
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Neuropeptide Y ◽  
Litter Size ◽  
High Fat Diet ◽  
Dietary Intervention ◽  
High Fat ◽  
Brown Adipose

Early life nutrition impacts on subsequent risk of obesity and hypertension. Several brain chemicals responsible for both feeding and cardiovascular regulation are altered in obesity. We examined effects of early postnatal overnutrition on blood pressure, brain neuropeptide Y (NPY), and adiposity markers. Rat pup litters were adjusted to either 3 or 12 male animals (overnutrition and control, respectively) on day 1 of life. After weaning, rats were given either a palatable high-fat diet or standard chow. Smaller litter pups were significantly heavier by 17 days of age. By 16 wk, the effect of litter size was masked by that of diet, postweaning. Small and normal litter animals fed a high-fat diet had similar increases in body weight, plasma insulin, leptin, and adiponectin concentrations, leptin mRNA, and fat masses relative to chow-fed animals. An increase in 11β-hydroxysteroid dehydrogenase-1 mRNA in white adipose tissue, and a decrease in uncoupling protein-1 mRNA in brown adipose tissue in both small litter groups at 16 wk of age, may represent a programming effect of the altered litter size. NPY concentration in the paraventricular nucleus of the hypothalamus was reduced in high fat-fed groups. Blood pressure was significantly elevated at 13 wk in high-fat-fed animals. This study demonstrates that overnourishment during early postnatal development leads to profound changes in body weight at weaning, which tended to abate with maturation. Thus the effects of long-term dietary intervention postweaning can override those of litter size-induced obesity.

scholarly journals Dietary curcumin supplement promotes browning and energy expenditure in postnatal overfed rats

2020 ◽  
Author(s):  
Xiaolei Zhu ◽  
Susu Du ◽  
Qinhui Yan ◽  
Cuiting Min ◽  
Nan Zhou ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Blood Lipid ◽  
Standard Diet ◽  
Mrna Levels ◽  
Lower Body Weight ◽  
Normal Feeding

Abstract Background: Early postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following with white adipose tissue (WAT) gain throughout life. This research was to investigate whether curcumin (CUR) supplement could promote WAT browning and activate thermogenesis in postnatal overfed rats.Methods and results: This study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), the SL rats were fed with a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplement had lower body weight and less WAT gain, had increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, increased respiratory exchange ratio (RER) and heat generation were consistent with expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not of the SL1% CUR rats. In addition, 2% CUR dietary supplement enhanced the serum norepinephrine (NE) levels in SL rats, with the upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT.Conclusion: Dietary CUR supplement attenuates body weight gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplement.

scholarly journals Effect of Insulin Resistance on Lipolytic activity of Adipose Tissue in Male Rats

2012 ◽  
Vol 1 (2) ◽  
pp. 68-73
Author(s):  
R Eldeeb ◽  
MH Gamal-Eldin ◽  
EA Khowailed ◽  
MM Fathy ◽  
N Shantakumari ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Lipolytic Activity ◽  
Fasting Blood Glucose ◽  
Significant Rise ◽  
Male Rats ◽  
Visceral Adipose

Background: The excess usage of fructose as a sweetener has raised the incidence of insulin resistance among the population which is associated with dyslipedemia, hypertension and obesity. This work studied the effect of induced insulin resistance on body weight, blood pressure, lipid profile, glycemic state and lipolytic activity of adipose tissue in male rats. Methods: Twenty male rats of 129.4 g average body weight (BW) were divided equally into two groups. Both had free access to water. The control group had pure water; the experimental group had water mixed with 25% of fructose to induce insulin resistance. After 3 months body weight, blood pressure, fasting blood glucose, insulin levels, lipid profile of both groups were measured and lipolytic activity of adipose tissue was assessed. Results: Rats given fructose for 3 months showed significant increase in BW, systolic blood pressure, triglyceride, Cholesterol, low density lipoprotein, fasting blood glucose and insulin levels with a significant decline in highdensity lipoprotein. Lipolytic activity of subcutaneous (SC) and visceral adipose tissue in presence of adrenaline increased significantly which runs in parallel with the results obtained in presence of insulin as it showed a significant rise in both SC and visceral adipose tissue. Data were considered statistically significant at alpha level of 5%. Conclusion: Insulin resistance induced in male rat by high fructose consumption showed a significant rise in BW and is associated with hypertension and dyslipidemia with significant rise in lipolytic activity of both SC and visceral adipose tissue. DOI: http://dx.doi.org/10.3126/njms.v1i2.6602 Nepal Journal of Medical Sciences. 2012;1(2): 68-73

Abstract 023: Inducible Deletion of Adipocyte Prorenin Receptor Reverses Obesity Related Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Eva Gatineau ◽  
Dianne Cohn ◽  
Ming Gong ◽  
Frédérique Yiannikouris
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Fat Mass ◽  
High Fat Diet ◽  
Standard Diet ◽  
Mrna Levels ◽  
High Fat ◽  
Elevated Systolic Blood Pressure ◽  
Prorenin Receptor

Obesity contributes to approximatively 2.5 million deaths every year and is associated with life threatening conditions including hypertension. Recently, we found that constitutive deletion of adipocyte (pro)renin-receptor (PRR) prevented high-fat diet-induced obesity through a drastic decrease in fat mass. However, adipocyte PRR deficient mice were characterized by a fatty liver and by an elevated systolic blood pressure (SBP), classic features of models of lipodystrophy. The purpose of this study was to investigate whether the temporally-controlled deletion of adipocyte PRR in obese mice reverses obesity related hypertension. After 18 weeks of high fat diet, inducible adipocyte-PRR deficient ( PRR ERT ) and control ( PRR fl/Y ) male mice (n=7-11 mice/ group) were injected intraperitoneally with tamoxifen (TMX) for 5 consecutive days. Body weight, body composition and blood pressure, measured by radiotelemetry in a subgroup of mice (n=2-4 mice/ group), were recorded before and after TMX injection. The inducible deletion of adipocyte PRR in PRR ERT mice decreased significantly body weights ( PRR fl/fl , 46.6 ± 1.3 g; PRR ERT , 42.1 ± 1.4 g, P<0.05) and fat mass ( PRR fl/fl , 15.8 ± 1.0 g; PRR ERT , 8.1 ± 0.7 g, P<0.05) compared to control mice. PPARγ, FABP4 and FAS mRNA levels were significantly decreased by 68% (6.8 out 10), 80% (8 out 10) and 68% (6.8 out 10) respectively in white adipose tissues of PRR ERT mice suggesting that PRR positively regulated adipogenesis and lipid metabolism in adipose tissue. In addition, the inducible deletion of adipocyte PRR in PRR ERT mice decreased significantly SBP compared to control mice ( PRR fl/fl , -4.3 ± 3.2 g; PRR ERT , -10.2 ± 2.4 g, P<0.05). Interestingly, adipocyte angiotensinogen mRNA abundance was significantly decreased in adipose tissue of PRR ERT mice fed a standard diet suggesting that the decrease in blood pressure might be mediated by a local renin angiotensin system (RAS). The measurement of local (liver, kidney, adipose tissue and brain) and systemic RAS in HF-fed mice is under investigation. Taken together, our results highlight a new signaling pathway in which PRR regulates adipogenesis, lipid metabolism and blood pressure. PRR could represent a new potential therapeutic target for obesity and hypertension.

scholarly journals Gsα deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight

2015 ◽  
Vol 113 (2) ◽  
pp. 446-451 ◽  
Author(s):  
Yong-Qi Li ◽  
Yogendra B. Shrestha ◽  
Min Chen ◽  
Tatyana Chanturiya ◽  
Oksana Gavrilova ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Energy Balance ◽  
Glucose Metabolism ◽  
Lipid Synthesis ◽  
Whole Body ◽  
Standard Diet ◽  
Fatty Acid Binding ◽  
Brown Adipose

Gsα, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsα deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis. In addition, Ad-GsKO mice maintained at thermoneutrality on a standard diet also had normal energy balance. Ad-GsKO mice had improved insulin sensitivity and glucose metabolism, possibly secondary to the effects of reduced lipolysis and lower circulating fatty acid binding protein 4 levels. Gsα signaling in adipose tissues may therefore affect whole-body glucose metabolism in the absence of an effect on body weight.

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