36 research outputs found
Ovariectomy and chronic stress lead toward leptin resistance in the satiety centers and insulin resistance in the hippocampus of Sprague- Dawley rats
Aim To evaluate the changes in the expression level of
gonadal steroid, insulin, and leptin receptors in the brain
of adult Sprague-Dawley female rats due to ovariectomy
and/or chronic stress.
Methods Sixteen-week-old ovariectomized and non-ovariectomized
female Sprague-Dawley rats were divided in
two groups and exposed to three 10-day-sessions of sham
or chronic stress. After the last stress-session the brains
were collected and free-floating immunohistochemical
staining was performed using androgen (AR), progesterone
(PR), estrogen-Ī² (ER-Ī²), insulin (IR-Ī±), and leptin receptor
(ObR) antibodies. The level of receptors expression was
analyzed in hypothalamic (HTH), cortical (CTX), dopaminergic
(VTA/SNC), and hippocampal regions (HIPP).
Results Ovariectomy downregulated AR in the hypothalamic
satiety centers and hippocampus. It prevented or
attenuated the stress-specific upregulation of AR in these
regions. The main difference in stress response between
non-ovariectomized and ovariectomized females was in
PR level. Ovariectomized ones had increased PR level in the
HTH, VTA, and HIPP. Combination of stressors pushed the
hypothalamic satiety centers toward the rise of ObR and
susceptibility to leptin resistance. When exposed to combined
stressors, the HIPP, SNC and piriform cortex upregulated
the expression of IR-Ī± and the possibility to develop
insulin resistance.
Conclusion Ovariectomy exacerbates the effect of chronic
stress by preventing gonadal receptor-specific stress response
reflected in the up-regulation of AR in the satiety
and hippocampal regions, while stress after ovariectomy
usually raises PR. The final outcome of inadequate stress
response is reflected in the upregulation of ObR in the satiety
centers and IR-Ī± in the regions susceptible to early
neurodegeneration. We discussed the possibility of stress
induced metabolic changes under conditions of hormone
deprivatio
Primjena metformina i liraglutida utjeÄe na strukturu hipokampusnih gangliozida u modelu Å”takora na dijeti obogaÄenoj mastima i ugljikohidratima
Insulin resistance has many deleterious effects on the central nervous system, including
the initiation and potentiation of neurodegeneration. While the pathogenesis of Alzheimerās disease
has been extensively researched with many insights into the effects of amyloids and neurofibrillary tangles,
the connection between the two pathogenic entities has not yet been fully elucidated. Gangliosides
are commonly found in neuronal membranes and myelin, specifically in lipid rafts that have been linked
to pathological amyloidogenesis. In this study, 64 Sprague Dawley rats with equal sex distribution were
separated into four sex-specific groups, as follows: control group on standard diet; group on high-fat,
high-sugar diet (HFHSD); group on HFHSD treated with metformin; and group on HFHSD treated
with liraglutide. Free-floating immunohistochemistry of the rat hippocampi was performed to analyze
group-specific and sex-specific changes in the composition of the four most common gangliosides found
in neuronal membranes and myelin sheaths, GM1, GD1a, GD1b and GT1b. The groups on HFHSD
showed glucose tolerance impairment and body weight increase at the end of the experiment, whereas
the groups treated with pharmacotherapeutics had better insulin sensitivity and decreases in body weight
by the end of the experiment. Most changes were observed for GM1 and GD1b. Positive immunoreactivity
for GM1 was observed in the male group treated with liraglutide in regions where it is not physiologically
found. The changes observed following HFHSD and liraglutide treatment were suggestive
of ganglioside restructuring that might have implications on pathological amyloidogenesis. Metformin
treatment did not significantly alter the hippocampal ganglioside composition in either sex.Inzulinska rezistencija ima negativan uÄinak na srediÅ”nji živÄani sustav, ukljuÄujuÄi razvoj i potencijaciju neurodegenerativnih
promjena. Iako postoje brojna saznanja o patogenezi Alzheimerove bolesti u kontekstu amiloidnih depozita i
neurofibrilarnih vlakana, veza izmeÄu inzulinske rezistencije i Alzheimerove bolesti joÅ” uvijek nije u potpunosti razjaÅ”njena.
Gangliozidi su prisutni u membranama neurona i mijelinskim ovojnicama, osobito u sklopu lipidnih splavi, koje su identificirane
kao mjesto patoloŔke amiloidogeneze. Ukupno je 64 Sprague Dawley Ŕtakora jednake spolne distribucije podijeljeno
u Äetiri spolno specifiÄne skupine: kontrolnu skupinu na standardnoj dijeti, skupinu na dijeti obogaÄenoj mastima i ugljikohidratima
(HFHSD), skupinu na HFHSD uz lijeÄenje metforminom te skupinu na HFHSD uz lijeÄenje liraglutidom. Provedena
je free-floating imunohistokemijska analiza promjena Äetiri najzastupljenija gangliozida u neuronskim membranama
i mijelinskim ovojnicama: GM1, GD1a, GD1b i GT1b. Skupine na HFHSD pokazale su poremeÄenu toleranciju glukoze
te poveÄanje tjelesne mase na kraju eksperimenta, dok su skupine koje su primale farmakoterapeutike pokazale poboljÅ”anje
tolerancije glukoze te smanjenje tjelesne mase na kraju eksperimenta. NajviŔe promjena zabilježeno je kod gangliozida GM1
i GD1b. Pozitivna imunoreaktivnost za GM1 zabilježena je kod mužjaka koji su lijeÄeni liraglutidom i u regijama hipokampusa
gdje u fizioloÅ”kim uvjetima nisu prisutni. Promjene nakon HFHSD i lijeÄenja liraglutidom upuÄuju na restrukturiranje
hipokampusnih gangliozida, Å”to može imati implikacije za patoloÅ”ku amiloidogenezu. LijeÄenje metforminom nije znaÄajno
utjecalo na hipokampusnu strukturu gangliozida u oba spola
Obesity in pregnancy: a novel concept on the roles of adipokines in uterine contractility
Obesity is a global health problem even among pregnant
women. Obesity alters quality of labor, such as preterm labor,
prolonged labor, and higher oxytocin requirements
in pregnant women. The most important factors to play
a role in the altered gestational period and serve as drug
targets to treat the consequences are female sexual hormones,
calcium channels, adrenergic system, oxytocin,
and prostaglandins. However, we have limited information
about the impact of obesity on the pregnant uterine contractility
and gestation time. Adipose tissue, which is the
largest endocrine and paracrine organ, especially in obesity,
is responsible for the production of adipokines and various
cytokines and chemokines, and there are no reliable
data available describing the relation between body mass
index, glucose intolerance, and adipokines during pregnancy.
Recent data suggest that the dysregulation of leptin,
adiponectin, and kisspeptin during pregnancy contributes
to gestational diabetes mellitus and pre-eclampsia. A
preclinical method for obese pregnancy should be developed
to clarify the action of adipokines and assess their impact
in obesity. The deeper understanding of the adipokines-
induced processes in obese pregnancy may be a step
closer to the prevention and therapy of preterm delivery
or prolonged pregnancy. Gestational weight gain is one of
the factors that could influence the prenatal development,
birth weight, and adiposity of newborn
Plasma Content of Glucose, C-reactive Protein, Uric Acid and Cholesterol in Male, Female and Ovariectomized Rats upon Acute and Chronic Stress ā a Path for Development of Cardiovascular Diseases
To explore sex differences in cardiovascular function under stress, we analyzed plasma levels of glucose, C-reactive protein (CRP), uric acid and cholesterol in male, female and ovariectomized rats under acute and chronic stress. Glucose tolerance test (GTT) was performed in all rats before any stress was performed, as well as later in the chronic stress experiment. GTT in control animals showed the same trend as in chronically stressed. Male rats showed the highest plasma level of glucose and uric acid upon acute stress in comparison between the other two groups. Ovariectomized rats reached the highest concentration of plasma cholesterol during acute and chronic stress, respectively and also the highest plasma concentration of CRP during acute stress. Stress, as a risk factor of metabolic syndrome, affected biochemical parameters in males upon acute more than upon chronic stress, but the opposite was observed in female rats. Gender differences supported by ovariectomy show that stress managing could be affected by sexual hormones
Sex differences in oxidative stress level and antioxidative enzymes expression and activity in obese pre-diabetic elderly rats treated with metformin or liraglutide
Aim To determine the effects of metformin or liraglutide on
oxidative stress level and antioxidative enzymes gene ex
-
pression and activity in the blood and vessels of pre-diabet
-
ic obese elderly Sprague-Dawley (SD) rats of both sexes.
Methods Male and female SD rats were assigned to the
following groups: a) control group (fed with standard ro
-
dent chow); b) high-fat and high-carbohydrate diet
(HSHFD) group fed with HSHFD from 20-65 weeks of age;
c) HSHFD+metformin treatment (50 mg/kg/d s.c.); and d)
HSHFD+liraglutide treatment (0.3 mg/kg/d s.c). Oxidative
stress parameters (ferric reducing ability of plasma and
thiobarbituric acid reactive substances) and superoxide dis
-
mutase (SOD), catalase (CAT), and glutathione peroxidase
(GPx) activity and gene expression were determined from
serum, aortas, and surface brain blood vessels (BBV).
Results HSHFD increased body weight in both sexes com
-
pared with the control group, while liraglutide prevented
this increase. Blood glucose level did not change. The lira
-
glutide group had a significantly increased antioxidative ca
-
pacity compared with the HSHFD group in both sexes. The
changes in antioxidative enzymesā activities in plasma were
more pronounced in male groups. The changes in gene ex
-
pression of antioxidative enzymes were more prominent in
microvessels and may be attributed to weight gain preven
-
tion.
Conclusions Obesity and antidiabetic drugs caused sexrelated differences in the level of antioxidative parameters.
Liraglutide exhibited stronger antioxidative effects than
metformin. These results indicate that weight gain due to
HSHFD is crucial for developing oxidative stress and for in
-
hibiting antioxidative protective mechanism
Sex-specific chronic stress response at the level of adrenal gland modified sexual hormone and leptin receptors
Aim To compare cardiometabolic risk-related biochemical
markers and sexual hormone and leptin receptors in the
adrenal gland of rat males, non-ovariectomized females
(NON-OVX), and ovariectomized females (OVX) under
chronic stress.
Methods Forty six 16-week-old Sprague-Dawley rats were
divided into male, NON-OVX, and OVX group and exposed
to chronic stress or kept as controls. Weight, glucose tolerance
test (GTT), serum concentration of glucose, and cholesterol
were measured. Adrenal glands were collected at
the age of 28 weeks and immunohistochemical staining
against estrogen beta (ERĪ²), progesterone (PR), testosterone
(AR), and leptin (Ob-R) receptors was performed.
Results Body weight, GTT, serum cholesterol, and glucose
changed in response to stress as expected and validated
the applied stress protocol. Stressed males had significantly
higher number of ERĪ² receptors in comparison
to control group (P = 0.028). Stressed NON-OVX group had
significantly decreased AR in comparison to control group
(P = 0.007). The levels of PR did not change in any consistent
pattern. The levels of Ob-R increased upon stress in
all groups, but the significant difference was reached only
in the case of stressed OVX group compared to control
(P = 0.033).
Conclusion Chronic stress response was sex specific. OVX
females had similar biochemical parameters as males.
Changes upon chronic stress in adrenal gland were related
to an increase in testosterone receptor in females and decrease
in estrogen receptor in males
Disparities and relative risk ratio of preterm birth in six Central and Eastern European centers
Aim To identify characteristic risk factors of preterm birth
in Central and Eastern Europe and explore the differences
from other developed countries.
Method Data on 33 794 term and 3867 preterm births
(<37 wks.) were extracted in a retrospective study between
January 1, 2007 and December 31, 2009. The study took
place in 6 centers in 5 countries: Czech Republic, Hungary
(two centers), Romania, Slovakia, and Ukraine. Data on historical
risk factors, pregnancy complications, and special
testing were gathered. Preterm birth frequencies and relevant
risk factors were analyzed using Statistical Analysis
System (SAS) software.
Results All the factors selected for study (history of smoking,
diabetes, chronic hypertension, current diabetes,
preeclampsia, progesterone use, current smoking, body
mass index, iron use and anemia during pregnancy), except
the history of diabetes were predictive of preterm
birth across all participating European centers. Preterm
birth was at least 2.4 times more likely with smoking (history
or current), three times more likely with preeclampsia,
2.9 times more likely with hypertension after adjusting for
other covariates. It had inverse relationship with the significant
predictor body mass index, with adjusted risk ratio of
0.8 to 1.0 in three sites. Iron use and anemia, though significant
predictors of preterm birth, indicated mixed patterns
for relative risk ratio.
Conclusion Smoking, preeclampsia, hypertension and
body mass index seem to be the foremost risk factors of
preterm birth. Implications of these factors could be beneficial
for design and implementation of interventions and
improve the birth outcome
Impact of ovariectomy, high fat diet, and lifestyle modifications on oxidative/antioxidative status in the rat liver
Aim To estimate the impact of high fat diet and estrogen
deficiency on the oxidative and antioxidative status in the
liver of the ovariectomized rats, as well as the ameliorating
effect of physical activity or consumption of functional
food containing bioactive compounds with antioxidative
properties on oxidative damage in the rat liver.
Methods The study was conducted from November 2012
to April 2013. Liver oxidative damage was determined by
lipid peroxidation levels expressed in terms of thiobarbituric
acid reactive substances (TBARS), while liver antioxidative
status was determined by catalase (CAT), glutathione
peroxidase (GPx), glutathione S-transferase (GST), glutathione
reductase (GR) activities, and glutathione (GSH) content.
Sixty-four female Wistar rats were divided into eight
groups: sham operated and ovariectomized rats that received
either standard diet, high fat diet, or high fat diet
supplemented with cereal selenized onion biscuits or high
fat diet together with introduction of physical exercise of
animals.
Results High fat diet significantly increased TBARS content
in the liver compared to standard diet (P = 0.032, P = 0.030).
Furthermore, high fat diet decreased the activities of CAT,
GR, and GST, as well as the content of GSH (P < 0.050). GPx
activity remained unchanged in all groups. Physical activity
and consumption of cereal selenized onion biscuits
showed protective effect through increased GR activity in
sham operated rats (P = 0.026, P = 0.009), while in ovariectomized
group CAT activity was increased (P = 0.018) in rats
that received cereal selenized onion biscuits.
Conclusion Feeding rats with high fat diet was accompanied
by decreased antioxidative enzyme activities and increased
lipid peroxidation. Bioactive compounds of cereal
selenized onion biscuits showed potential to attenuate the
adverse impact of high fat diet on antioxidative statu