scholarly journals MON-028 Chronic Resveratrol Exposure Improves Glucose Homeostasis and Cardiac Function in a Rat Model of Polycystic Ovarian Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Rogelio Enrique Molina ◽  
Tiffany Shao ◽  
Harmanprit Randhawa ◽  
Vanessa Hoang ◽  
Arpita Kalla Vyas

Abstract Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age, with a prevalence of 5-8%. Long-term complications seen in PCOS include cardiovascular disease and type 2 Diabetes Mellitus. Current therapies do not completely address the cardiometabolic perturbations seen in women with PCOS. Resveratrol (RSV), a natural polyphenol, is shown to have beneficial cardio-metabolic effects in various pathological conditions including that on insulin sensitivity, cardiovascular function. In-vitro studies suggest it’s beneficial effects on ovarian function as well. Therefore, we hypothesized that chronic exposure to RSV would improve both cardiovascular and metabolic phenotypes in PCOS. To test this hypothesis we used an established rat model of PCOS that develops metabolic derangement and irregular cycles. A 7.5 mg (90-day release) dihydrotestosterone (DHT) pellet providing a daily dose of 83 mcg was implanted in 5-week-old female rats. Studies were also conducted on littermate matched controls (C) with no DHT implant. A subgroup of the control and DHT treated rats (n=6 per group) received a 0.84 g/kg dose of resveratrol (RSV) in their chow starting at age 5 weeks. At 8 weeks, animals were weighed weekly (n=6 per group). Oral glucose tolerance test (OGTT n=6 per group) and cardiac echocardiogram (C n=12, C+RSV n=6, DHT n=10, DHT+RSV n=6) were conducted at 16-weeks of age. Body weight increased significantly in DHT treated rats compared to C between 8 and 16 weeks (40 vs 22 grams, p <0.001). RSV treatment did not mitigate the effects of DHT on body weight (34 vs 40 grams, p>0.5). There was significantly higher glucose excursion at 30 minutes post glucose load in both DHT (148± 7.4 mg/dl) and DHT+RSV (139± 7.4 mg/dl) compared to C group (121± 13 mg/dl, p<0.001, p=0.03 respectively). However, by 60 and 90 minutes only DHT group had a significantly higher glucose excursion compared to both DHT+RSV and C groups (131± 4.1,124± 5.7,110 ± 5.9 mg/dl, p=0.015,p=0.21 respectively); 90min (118±5.8,110±4.7,96±4.2 mg/dl, p<0.01,p=0.09 respectively). By 120 minutes, no significant difference in glucose levels existed between groups. Cardiac echocardiogram showed significantly lower mitral valve E/A ratio (and increased MV isovolumic relaxation time (IVRT) in DHT group compared to C. RSV treatment reversed these changes. In conclusion, RSV improved glucose homeostasis and diastolic dysfunction in the DHT induced rodent model of PCOS and may serve as a novel treatment option targeting the cardiometabolic derangement seen in PCOS. Further studies elucidating the mechanisms underlying the beneficial effects of RSV on cardio-metabolic phenotype in this PCOS rodent model is warranted.

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Maryam Mosavat ◽  
Foong Kiew Ooi ◽  
Mahaneem Mohamed

This study was performed to determine the effects of 8-week honey supplementation combined with different jumping exercise intensities on serum cortisol, progesterone, estradiol, and reproductive organs. Eighty-four 9-week-old female rats were divided into 7 groups: baseline controls (C0), sedentary group (C), 20 and 80 jumps per day (Ex20J,Ex80J), honey (H), and combined honey with 20 and 80 jumps per day (HEx20J,HEx80J) groups. Jumping exercise was performed at 5 days/week and honey was given at a dosage of 1 g/kg body weight/day for 7 days/week. The level of serum cortisol was higher inEx20JandEx80Jcompared to C. There was significantly lower value of serum cortisol inHEx20Jcompared toEx80J. Serum progesterone levels were significantly lower inEx20JandEx80Jcompared to C. However, serum progesterone levels were significantly higher inHEx20JandHEx80Jcompared toEx20JandEx80J. Relative uterine weights were significantly greater inHEx20Jcompared to C andHEx80J, respectively. There was no significant difference in estradiol level and relative ovarian weights among all the groups. Therefore, honey elicited beneficial effects in reducing the increase of cortisol and in increasing the reduce of progesterone levels induced by different intensities jumping exercise in female rats.


Endocrinology ◽  
2021 ◽  
Author(s):  
Katharina Schnabl ◽  
Yongguo Li ◽  
Mueez U-Din ◽  
Martin Klingenspor

Abstract The obesity pandemic requires effective preventative and therapeutic intervention strategies. Successful and sustained obesity treatment is currently limited to bariatric surgery. Modulating the release of gut hormones is considered promising to mimic bariatric surgery with its beneficial effects on food intake, body weight and blood glucose levels. The gut peptide secretin was the first molecule to be termed a hormone; nevertheless, it only recently has been established as a legitimate anorexigenic peptide. In contrast to gut hormones that crosstalk with the brain either directly or by afferent neuronal projections, secretin mediates meal-associated brown fat thermogenesis to induce meal termination, thereby qualifying this physiological mechanism as an attractive, peripheral target for the treatment of obesity. In this perspective, it is of pivotal interest to deepen our yet superficial knowledge on the physiological roles of secretin as well as meal-associated thermogenesis in energy balance and body weight regulation. Of note, the emerging differences between meal-associated thermogenesis and cold-induced thermogenesis must be taken into account. In fact, there is no correlation between these two entities. In addition, the investigation of potential effects of secretin in hedonic-driven food intake, bariatric surgery as well as chronic treatment using suitable application strategies to overcome pharmacokinetic limitations will provide further insight into its potential to influence energy balance. The aim of this article is to review the facts on secretin’s metabolic effects, address prevailing gaps in our knowledge, and provide an overview on the opportunities and challenges of the therapeutic potential of secretin in body weight control.


Author(s):  
Camille Marciniak ◽  
Oscar Chávez-Talavera ◽  
Robert Caiazzo ◽  
Thomas Hubert ◽  
Lorea Zubiaga ◽  
...  

Background/Objectives: The alimentary limb has been proposed to be a key driver of the weight-loss-independent metabolic improvements that occur upon bariatric surgery. However, the One Anastomosis Gastric Bypass (OAGB) procedure, consisting of one long biliary limb and a short common limb, induces stronger beneficial metabolic effects compared to Roux-en-Y Gastric Bypass (RYGB) in humans, despite the lack of an alimentary limb. The aim of this study was to assess the role of the biliary and common limbs in the weight-loss and metabolic effects that occur upon OAGB. Subjects/Methods: OAGB and sham surgery, with or without modifications of the length of either the biliary limb or the common limb, were performed in Gottingen-like minipigs. Weight loss, metabolic changes, and the effects on plasma and intestinal bile acids (BAs) were assessed 15 days after surgery. Results: OAGB significantly decreased body weight, improved glucose homeostasis, increased postprandial GLP-1 and fasting plasma BAs, and qualitatively changed the intestinal BA species composition. Resection of the biliary limb prevented the body weight loss effects of OAGB and attenuated the postprandial GLP-1 increase. Improvements in glucose homeostasis along with changes in plasma and intestinal BAs occurred after OAGB regardless of the biliary limb length. Resection of only the common limb reproduced the glucose homeostasis effects and the changes in intestinal BAs. Conclusions: Our results suggest that the changes in glucose metabolism and BAs after OAGB are mainly mediated by the length of the common limb, whereas the length of the biliary limb contributes to body weight loss.


1985 ◽  
Vol 4 (1) ◽  
pp. 91-110 ◽  
Author(s):  
A. M. Hoberman ◽  
W. M. Weatherholtz ◽  
R. S. Durloo

The effects of a new experimental drug, KF-868, were investigated after administration to pregnant Sprague-Dawley rats at 0(vehicle), 0.1, 2.0, and 40.0 mg/kg per day during Days 7 through 17 of gestation by examination of term fetuses and naturally delivered offspring. Pregnant rats administered 0.1, 2.0, and 40.0 mg/kg per day gained significantly more weight during the dosage period than did the vehicle control group. Treatment-related physical signs, bloody crust on nose and stains on fur, were observed in the high dosage group. Fetal viability was significantly increased, and resorptions were significantly decreased for the mid and high dosage groups, when compared with the control group. Average fetal body weights for cesarean-delivered fetuses were less for the 40.0 mg/kg per day dosage groups than for the vehicle control group. Visceral and skeletal evaluations of fetuses revealed no difference between the control and test groups. Percent survival of pups was significantly less for the high dosage group than for the control group. Average rat body weights prior to mating for the high dosage group were generally less than for the control group. All physical and functional developmental values were comparable among the control and test groups. Evaluation of postweaning parameters of pups revealed no significant difference in sex maturation, behavior (open-field and water maze), and reproductive capacity. Average body weight gains during the 9-week growth period before mating were significantly less for the 40.0 mg/kg per day dosage group F1 generation female rats. Toxicity in fetuses and offspring was observed only at the highest dosage level. Dosage-dependent, significant increases in maternal body weight gain, as compared with control values, occurred for doses in the 3 KF-868-administered groups. These results indicate that 0.1 and 2.0 mg/kg per day dosages of KF-868 were not lethal and did not produce any adverse effects on the morphological or functional development of offspring. Toxicity was evident in offspring and fetuses of dams administered 40.0 mg/kg per day KF-868, 40,000 times as high as the daily therapeutic dose.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Sabiha İrem Ünal ◽  
Ayla Gulden Pekcan

AbstractNuts are good sources of dietary fiber, magnesium, polyunsaturated fats, vitamin E, and antioxidants, all of which may have health benefits and associated with increased sensations of satiety and could have beneficial effects on weight control. This study aims to determine the effects of a balanced hypocaloric almond (30 g/day) enriched diet (AED) compared to a balanced hypocaloric almond free diet (AFD) on anthropometric measurements and blood parameters. Study was a 3-months, randomized, controlled trial with four serial measurements on 32 overweight and obese (BMI: ≥ 25 kg/m2) women, aged 25–50 years. The subjects were randomly divided into two groups (16 AED and 16 AFD). Individualized hypocaloric diets of AED considering the energy recommendation, 30 g/day of almonds was added as a snack. Demographic characteristics, nutritional habits, physical activity levels of subjects were determined by a questionnaire. 24-hour dietary intakes for 3 consecutive days (one day week-end) were recorded at the beginning, 1rd, 2nd, and 3rd months of the study. Anthropometric measurements (height, body weight, waist, hip and neck circumferences) were taken and body composition was determined by Bioelectrical Impedance Analysis (BIA), BMI, waist/hip circumference ratio (WHR) and waist circumference/height ratio (WHtR) were calculated. Fasting blood glucose, insulin level, HbA1c, HOMA-IR, total cholesterol, triglycerides, serum iron, haemoglobin, TSH, CRP were determined prior to and at the end (3rd month) of the study. At the beginning of the study no statistically significant difference was found between anthropometric measurements of the groups (p > 0.05). Body weight, BMI, waist, hip circumferences, WHR, WHtR, percentage of body fat, body fat mass were decreased significantly in almond and control groups compared with the beginning and 1rd, 2nd., 3rd months of the study (p = 0.001). Significant reductions in HbA1c and LDL-cholesterol levels were determined in almond group (p < 0.05). Statistically significant differences were found in insulin, HDL-cholesterol, triglycerides and HOMA-IR levels compared to the prior and end of study in both groups (p < 0.05). Balanced hypocaloric diet caused weight loss and improvements in anthropometric and blood parameters in both groups, but better improvement was determined with almond enriched diet. Almonds as a snack could be recommended as a healthy choice in weight reduction diets. Almonds fiber and protein content may have beneficial effects on weight reduction.


2011 ◽  
Vol 3 (3) ◽  
pp. 143-150
Author(s):  
Hatice Işık ◽  
Ozlem Moraloglu ◽  
Sevtap Kilic ◽  
Ali Seven ◽  
Muzaffer Caydere ◽  
...  

Aim Angiogenesis plays an important role in the pathogenesis of endometriosis. Thus, the inhibition of angiogenesis may prevent endometriosis. Bevacizumab is a recombinant humanized monoclonal antibody against VEGF. The aim of this study is to investigate the efficacy of anti-VEGF therapy on the prophylaxis and treatment of endometriotic foci in a rat model. Methods This experimental study is prospective, randomized, and placebo-controlled. Thirty-six Wistar-Albino female rats were divided into 3 groups. Experimental endometriosis was induced by the implantation of autologous endometrial tissue. The bevacizumab administration route was intraperitoneal. Group A was the prophylaxis group; Group B was the treatment group, and Group C was the control group. The volumes of the implants as well as their VEGF and Ki-67 immunohistochemical staining are main outcome measures. Results The volumes of the lesions were smaller in Group A than Group C [P<.05]. The volumes of endometriotic foci in Group B were smaller than in Group C [P<.05]. Bevacizumab caused regression and atrophy of the endometriotic lesions. After the treatment the histopathologic and immunohistochemical scores in Group B were less than before treatment and less than the scores in Group C. Conclusions Bevacizumab treatment had a regressive effect on the endometriotic implants. As an anti-VEGF agent, bevacizumab has beneficial effects on the prophylaxis and treatment of endometriosis.


Author(s):  
Carlos M Castorena ◽  
Alexandre Caron ◽  
Natalie J Michael ◽  
Newaz I Ahmed ◽  
Amanda G Arnold ◽  
...  

Cannabinoid 1 receptor (CB1R) inverse-agonists reduce body weight and improve several parameters of glucose homeostasis. However, these drugs have also been associated with deleterious side effects. CB1R expression is widespread in the brain and in peripheral tissues, but whether specific sites of expression can mediate the beneficial metabolic effects of CB1R drugs, while avoiding the untoward side effects, remains unclear. Evidence suggests inverse-agonists may act on key sites within the central nervous system to improve metabolism. The ventromedial hypothalamus (VMH) is a critical node regulating energy balance and glucose homeostasis. To determine the contributions of CB1Rs expressed in VMH neurons in regulating metabolic homeostasis, we generated mice lacking CB1Rs in the VMH. We found that deletion of CB1Rs in the VMH did not affect body weight in male and female mice fed chow or HFD. We also found that deletion of CB1Rs in the VMH did not alter weight loss responses induced by the CB1R inverse-agonists SR141716. However, we did find that CB1Rs of the VMH regulate parameters of glucose homeostasis independent of body weight in diet-induced obese male mice.


1989 ◽  
Vol 257 (6) ◽  
pp. R1417-R1422 ◽  
Author(s):  
S. Rivest ◽  
Y. Deshaies ◽  
D. Richard

The purpose of this study was to investigate the effects of a chronic intracerebroventricular administration of corticotropin-releasing factor (CRF) on energy balance of male and female rats. One week after their delivery to the laboratory, both male and female rats were divided into two groups. One group in each sex was treated with human/rat CRF, while another group was infused with the vehicle. Chronic administration of CRF was accomplished by means of miniosmotic pumps connected to a cannula that was stereotaxically directed into the third ventricle. Food intake and body weight were measured each day during the study. After 14 days of treatment, the rats were killed by decapitation. Energy, fat, and protein contents of the carcasses were quantified. Serum testosterone and estradiol were assayed in males and females, respectively. Administration of CRF significantly reduced body weight gain and food intake in male rats. No significant difference in those variables was observed between female rats treated with CRF and their controls infused with saline. Similarly, metabolizable energy intake and body energy gain were reduced in male rats infused with CRF, whereas no difference was observed between female animals treated with CRF and those infused with saline. In male rats, body fat and body protein contents were lower in CRF-treated than in saline-infused rats. In female rats, CRF did not affect body composition. Serum testosterone in male rats and serum estradiol in female animals were reduced after chronic infusion of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)


2015 ◽  
Vol 308 (12) ◽  
pp. E1076-E1084 ◽  
Author(s):  
Ilana B. Ressler ◽  
Bernadette E. Grayson ◽  
Yvonne M. Ulrich-Lai ◽  
Randy J. Seeley

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Although a comorbidity of PCOS is obesity, many are lean. We hypothesized that increased saturated fat consumption and obesity would exacerbate metabolic and stress indices in a rodent model of PCOS. Female rats were implanted with the nonaromatizable androgen dihydrotestosterone (DHT) or placebo pellets prior to puberty. Half of each group was maintained ad libitum on either a high-fat diet (HFD; 40% butter fat calories) or nutrient-matched low-fat diet (LFD). Irrespective of diet, DHT-treated animals gained more body weight, had irregular cycles, and were glucose intolerant compared with controls on both diets. HFD/DHT animals had the highest levels of fat mass and insulin resistance. DHT animals demonstrated increased anxiety-related behavior in the elevated plus maze by decreased distance traveled and time in the open arms. HFD consumption increased immobility during the forced-swim test. DHT treatment suppressed diurnal corticosterone measurements in both diet groups. In parallel, DHT treatment significantly dampened stress responsivity to a mild stressor. Brains of DHT animals showed attenuated c-Fos activation in the ventromedial hypothalamus and arcuate nucleus; irrespective of DHT-treatment, however, all HFD animals had elevated hypothalamic paraventricular nucleus c-Fos activation. Whereas hyperandrogenism drives overall body weight gain, glucose intolerance, anxiety behaviors, and stress responsivity, HFD consumption exacerbates the effect of androgens on adiposity, insulin resistance, and depressive behaviors.


2021 ◽  
Vol 12 (5) ◽  
pp. 6428-6436

Methadone Maintenance Therapy (MMT) has been accepted as a gold-standard treatment for opioid therapy. It may associate with adverse effects. This study aimed to affect methadone on serum lipid profile, leptin levels, and liver enzymes in male and female rats. 41 Wistar rats weighing 200-300gr were randomly assigned into four groups, including two methadone treatments and two control groups, both male and female, that received 5mg/kg methadone or 1cc normal saline daily for 8 weeks respectively by gavage method. All animals were weighed weekly. Fasting blood sugar (FBS) was measured by a glucometer, and blood samples were taken by cardiac puncture for triglyceride, low-density lipoprotein (LDL),high-density lipoprotein (HDL), total cholesterol, Aspartate transaminase (AST), Alanine transaminase (ALT), alkaline phosphatase (ALP) and leptin levels measurement after 12h fasting. One-way ANOVA showed no significant difference in mean FBS, total cholesterol, triglyceride, and LDL levels among the four groups. Moreover, there was a statistically significant difference in the mean of HDL, ALT, AST, and ALP levels. Furthermore, repeated measures ANOVA indicated a significant increase in body weight of rats during 8 weeks. Our findings indicated changes in some metabolic effects associated with methadone treatment in a gender-dependent manner.


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