Long-term effects of exogenous leptin on body weight and fat in post-obese female rats

2001 ◽  
Vol 74 (3) ◽  
pp. 321-328 ◽  
Author(s):  
Anne Buison ◽  
Frank Ordiz ◽  
K.-L.Catherine Jen
2021 ◽  
Author(s):  
Robert Phillips ◽  
Deborah Jaffey ◽  
Terry Powley

Electrical stimulation is a potential therapy for gastric disorders. Here we describe our surgical procedure for the implantation of patch electrodes on the muscle wall of the stomach of both male and female rats for use in chronic studies looking at the long-term effects of stimulation on physiology and behavior. The surgery is well tolerated by the subjects as rats return to pre-surgical body weight and normal solid chow intake within 7 to 10 days post-surgery. In our hands, rats implanted using the methods described below have been continuously run in feeding and motility experiments for 8 to 12 weeks with minimal to no loss of subjects. When failure does occur, it is typically a result of back mount failure at the site of attachment of the overhead tether to the back mount.


Author(s):  
Kendrick Lee ◽  
Steven R. Laviolette ◽  
Daniel B. Hardy

Abstract Background Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and 21. Heart tissue was harvested from the offspring at 3 weeks for molecular analysis of cardiac remodelling. Results Exposure to Δ9-THC during pregnancy led to FGR with a significant decrease in heart-to-body weight ratios at birth. By 3 weeks, pups exhibited catch-up growth associated with significantly greater left ventricle anterior wall thickness with a decrease in cardiac output. Moreover, these Δ9-THC-exposed offsprings exhibited increased expression of collagen I and III, decreased matrix metallopeptidase-2 expression, and increased inactivation of glycogen synthase kinase-3β, all associated with cardiac remodelling. Conclusions Collectively, these data suggest that Δ9-THC-exposed FGR offspring undergo postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function early in life. Impact To date, the long-term effects of perinatal Δ9-THC (the main psychoactive component) exposure on the cardiac function in the offspring remain unknown. We demonstrated, for the first time, that exposure to Δ9-THC alone during rat pregnancy results in significantly smaller hearts relative to body weight. These Δ9-THC-exposed offsprings exhibited postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function. Given the increased popularity of cannabis use in pregnancy along with rising Δ9-THC concentrations, this study, for the first time, identifies the risk of perinatal Δ9-THC exposure on early postnatal cardiovascular health.


1989 ◽  
Vol 123 (1) ◽  
pp. 83-91 ◽  
Author(s):  
K.-L. Kolho ◽  
I. Huhtaniemi

ABSTRACT The acute and long-term effects of pituitary-testis suppression with a gonadotrophin-releasing hormone (GnRH) agonist, d-Ser(But)6des-Gly10-GnRH N-ethylamide (buserelin; 0·02, 0·1, 1·0 or 10 mg/kg body weight per day s.c.) or antagonist, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10-GnRH (RS 68439; 2 mg/kg body weight per day s.c.) were studied in male rats treated on days 1–15 of life. The animals were killed on day 16 (acute effects) or as adults (130–160 days; long-term effects). Acutely, the lowest dose of the agonist decreased pituitary FSH content and testicular LH receptors, but with increasing doses pituitary and serum LH concentrations, intratesticular testosterone content and weights of testes were also suppressed (P< 0·05–0·01). No decrease was found in serum FSH or in weights of accessory sex organs even with the highest dose of the agonist, the latter finding indicating continuing secretion of androgens. The GnRH antagonist treatment suppressed pituitary LH and FSH contents and serum LH (P< 0·05–0·01) but, as with the agonist, serum FSH remained unaltered. Testicular testosterone and testis weights were decreased (P <0·01) but testicular LH receptors remained unchanged. Moreover, the seminal vesicle and ventral prostate weights were reduced, in contrast to the effects of the agonists. Pituitary LH and FSH contents had recovered in all adult rats treated neonatally with agonist and there was no effect on serum LH and testosterone concentrations or on fertility. In contrast, in adult rats treated neonatally with antagonist, weights of testis and accessory sex organs remained decreased (P <0·01–0·05) but hormone secretion from the pituitary and testis had returned to normal except that serum FSH was increased by 80% (P <0·01). Interestingly, 90% of the antagonist-treated animals were infertile. It is concluded that treatment with a GnRH agonist during the neonatal period does not have a chronic effect on pituitary-gonadal function. In contrast, GnRH antagonist treatment neonatally permanently inhibits the development of the testis and accessory sex organs and results in infertility. Interestingly, despite the decline of pituitary FSH neonatally, neither of the GnRH analogues was able to suppress serum FSH values and this differs from the concomitant changes in LH and from the effects of similar treatments in adult rats. Journal of Endocrinology (1989) 123, 83–91


2000 ◽  
Vol 19 (8) ◽  
pp. 434-439 ◽  
Author(s):  
C E M van Gelderen ◽  
J A Bijlsma ◽  
W van Dokkum ◽  
T J F Savelkoull

Because from earlier experiments in rats and a pilot study in humans a no effect level of glycyrrhizic acid could not be established, a second experiment was performed in healthy volunteers. The experiment was performed in females only, because the effects were most marked in females in the pilot study. Doses of 0, 1, 2 and 4 mg glycyrrhizic acid/kg body weight were administered orally for 8 weeks to 39 healthy female volunteers aged 19-40 years. The experimentlasted 12 weeks including an adaptation and a “wash-out” period.Ano-effectlevel of2 mg/kgis proposed from the results ofthis study, from which an acceptable daily intake (ADI) of 0.2 mg/kg body weight can be extrapolated with a safety factor of 10. This means consumption of 12 mg glycyrrhizic acid/day for a person with a body weight of 60 kg. This would be equal to 6 g licorice a day, assuming that licorice contains 0.2% of glycyrrhizic acid. The proposed ADI is below the limit advised by the Dutch Nutrition Council of 200 mg glycyrrhizic acid/day. This reflects the relatively mild acute toxicity of glycyrrhizic acid, which is also emphasised by the “generally recognised as safe” (GRAS) status of glycyrrhizic acid in the USA in 1983. However, the long-term effects of a mild chronic intoxication (causing, for example, a mild hypertension), although not immediately lethal, justify special attention to the amount of glycyrrhizic acid used daily.


2021 ◽  
Vol 22 (16) ◽  
pp. 8899
Author(s):  
Marina Gabaglio ◽  
Erica Zamberletti ◽  
Cristina Manenti ◽  
Daniela Parolaro ◽  
Tiziana Rubino

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission.


2017 ◽  
Vol 34 (03) ◽  
pp. 156-167
Author(s):  
A. Nyongesa ◽  
N. Patel ◽  
E. Wango ◽  
D. Onyango

Abstract Introduction: This study investigated short- and long-term effects of khat (Catha edulis) on hypophyseal, epididymal and testicular morphology, body weight and temperature changes and haematological parameters of rabbits. Materials and Methods: Twenty five male New Zealand White rabbits, divided into five groups were used. First four groups were administered, via intra-gastric tube, 1.5, 4.5, 13.5 and 40.5 g/kg body weight respectively of khat extract thrice a week for 8 weeks while controls received normal saline. Short-term and long-term effects were evaluated for hypophyseal, epididymal and testicular morphology, body temperature as well as body weight changes, food consumption and haematological parameters. Data on haematological parameters, body weight changes, body temperature and food consumption was done using one-way ANOVA at 95% confidence interval using SPSS version 12.0. Results: There was vacuolation in spermatogonia and spermatocytes at high doses while epididymides and hypophyses were unaffected. A significant decrease (P<0.05) in body weight of treatment groups correlated with reduced food intake with increasing doses and chronicity of exposure. Packed cell volume, red blood cell count and haemoglobin concentration decreased while white blood cell count increased with increasing doses. Conclusion: Khat extract had direct effects on spermatogenesis compounded by poor body weight gain, hyperthermia and blood volume loss.


1976 ◽  
Vol 71 (1) ◽  
pp. 109-114 ◽  
Author(s):  
I. DONIACH ◽  
D. J. SHALE

SUMMARY From the differences in radiation profiles between 131I and 125I isotopes of iodine it would be expected that they would show different effects on thyroid function. The differences should lead to lower rates of thyroid gland destruction with 125I and hence less post-irradiation hypothyroidism. This difference in biological effect has been demonstrated in rats by indirect assessment of thyroid function. In this report the long-term effects of a range of similar doses of 131I and 125I were compared, in male and female rats, by direct assessment of thyroid function. Seventeen months after receiving 25 and 125 μCi of 131I, male and female rats showed significant elevation of serum TSH concentration and a reduction in 3 h radioiodine uptake. Rats receiving 1 and 5 μCi of 131I and all doses of 125I showed no significant changes in thyroid function. These findings confirm the previously reported differences in effect between the 131I and 125I isotopes of iodine in the rat.


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