首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Obesity is a metabolic disorder that predisposes to numerous diseases and has become a major global public health concern. Cafeteria diet (CAF) is the animal model used for the study of obesity that more closely reflects Western diet habits. Previously, we described that CAF administration for 60 days induces obesity in female rats and their fetuses develop macrosomia. Given that, in our model, rats are not genetically modified and that obese mothers were fed standard chow during pregnancy, the aim of the current study was to test the hypothesis that obesity alters the intrauterine environment prior to pregnancy, and this may explain the exacerbated fetal weight gain. We found that uteri from obese rats during the estrous phase developed insulin resistance through mechanisms that involve the induction of uterine hypoxia and the down-regulation of the insulin receptor gene. Moreover, uterine cell proliferation was induced by obesity concomitantly with the reduction in the uterine contractile response to a β2 AR agonist, salbutamol, and this may be consequence of the down-regulation in the uterine β2 AR expression. We conclude that CAF-induced obesity alters the uterine environment in rats during the estrous phase and may cause the fetal macrosomia previously described by us in obese animals. The lower sensitivity of the uterus to a relaxation stimulus (salbutamol) is not a minor fact given that for implantation to occur the uterus must be relaxed for embryo nidation. Thus, the alteration in the uterine quiescence may impair implantation and, consequently, the foregoing pregnancy.  相似文献   

3.
Rat or hamster pups exposed to constant light or darkness since birth exhibit many circadian rhythms synchronized with those of the mother. During early development, a number of cues derived from the maternal circadian system synchronize the fetal and neonatal circadian clock. Maternal pineal sympathetic denervation during early pregnancy disrupts maternal synchronization of parotid α-amylase and testicular malate dehydrogenase circadian rhythms in rat pups. Maternal pineal sympathetic denervation was used to study potential agents able to synchronize the fetal or neonatal circadian clock. Melatonin injection to denervated pregnant mothers prevents the pineal sympathetic denervation effect on those circadian rhythms. We now studied the synchronizing effect of a benzodiazepine compound, diazepam. This GABAA agonist synchronized testicular malate dehydrogenase (MDH) activity of pups when it was injected to sympathetic denervated pregnant dams (a daily dose at 07:00 or 19:00 h from the 14 th to the 20 th day of gestation) or orally administered to the pups (a daily dose at 19:00 h from the 10 th to 24 th day of life). Co-injection of diazepam and GABAA antagonist, flumazenil, blocked the synchronizing effect of diazepam. The results demonstrate that diazepam has a synchronizing effect on the development of the circadian clock in rats and suggest that modulation of maternal GABAA could participate in mammalian maternal synchronization.  相似文献   

4.
Obesity during pregnancy programs adult-onset heart disease in the offspring. Clinical studies indicate that exposure to an adverse environment in utero during early, as compared to late, gestation leads to a higher prevalence of adult-onset heart disease. This suggests that the early developing heart is particularly sensitive to an adverse environment. Accordingly, growing evidence from clinical studies and animal models demonstrates that obesity during pregnancy alters the function of the fetal heart, programming a higher risk of cardiovascular disease later in life. Moreover, gene expression patterns and signaling pathways that promote initiation and progression of cardiovascular disease are altered in the hearts in offspring born to obese mothers. However, the mechanisms mediating the long-term effects of an adverse environment in utero on the developing heart leading to adult-onset disease are not clear. Here, we review clinical and experimental evidence documenting the effects of maternal obesity during pregnancy on the fetal and post-natal heart and emphasize on the potential mechanisms of disease programming.  相似文献   

5.
Animal studies demonstrate that circadian rhythm disruption during pregnancy can be deleterious to reproductive capacity and the long-term health of the progeny. Our previous studies in rats have shown that exposure of pregnant dams to an environment that significantly disrupts maternal circadian rhythms programs increased adiposity and poor glucose metabolism in offspring. In this study, we used mice with a ClockΔ19 mutation to determine whether foetal development within a genetically disrupted circadian environment affects pregnancy outcomes and alters the metabolic health of offspring. Ten female ClockΔ19+MEL mutant mice were mated with 10 wildtype males, and 10 wildtype females were mated with 10 ClockΔ19+MEL mutant males. While genetically identical, the heterozygote foetuses were exposed to either a normal (wildtype dams) or disrupted (ClockΔ19+MEL mutant dams) circadian environment during gestation. Pregnancy outcomes including time to mate, gestation length, litter size and birth weight were assessed. One male and one female offspring from each litter were assessed for postnatal growth, body composition, intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test at 3 and 12 months of age. There was no effect of maternal genotype on pregnancy outcomes, with days to plug, gestation length, litter size and perinatal mortality not significantly different between wildtype and ClockΔ19+MEL mutant dams. Similarly, there was no effect of maternal genotype on weight of the offspring at birth or at any stage of postnatal growth. While there was an effect of sex on various tissue weights at 3 and 12 months of age, there were minimal effects of maternal genotype. Relative adrenal weight was significantly reduced (?32%) in offspring from ClockΔ19+MEL mutant dams, whereas gastrocnemius muscle was significantly increased (+16%) at 3 months of age only. Intraperitoneal glucose tolerance tests at 3 months of age revealed female offspring from ClockΔ19+MEL mutant dams had significantly reduced area under the curve following glucose administration (?25%), although no differences were found at 12 months of age. There was no effect of maternal genotype on intraperitoneal insulin tolerance at 3 or 12 months of age for either sex. These results demonstrate that foetal growth within a genetically disrupted circadian environment during gestation has no effect on pregnancy success, and only marginal impacts upon the long-term metabolic health of offspring. These results do not support the hypothesis that circadian rhythm disruption during pregnancy programs poor metabolic homeostasis in offspring. However, when maintained on a 12L:12D photoperiod, the ClockΔ19+MEL mutant dams display relatively normal patterns of activity and melatonin secretion, which may have reduced the impact of the mutation upon foetal metabolic programming.  相似文献   

6.
The impact of pregnancy and lactation on ultradian rhythms (URs) and circadian rhythms (CRs) of locomotor activity was assessed in circadian rhythmic and arrhythmic Siberian hamsters maintained in a long-day photoperiod (16 h light/day). Progressive decrements in CR robustness and amplitude over the course of gestation were accompanied by enhanced URs. Dark-phase UR period and amplitude increased during early gestation and complexity and robustness increased during late gestation. The persistence of pregnancy-associated enhancements of URs in circadian arrhythmic (ARR) hamsters suggests that reproductive modulation of the UR waveform is not dependent on coherent circadian organization. The increased incidence of dark-phase URs appeared more rapidly in ARR dams than entrained (ENTR) dams. Throughout gestation, the percentage of dams with dark-phase URs was significantly greater in the ARR group. Gestational increases in UR complexity and robustness emerged earlier and were greater in ARR than ENTR dams. The attenuation of CRs during lactation is correlated with increased expression of URs. Relaxation of circadian control of the dam's behavior may increase fitness by permitting more efficient interactions with circadian arrhythmic pups.  相似文献   

7.
Obesity constitutes a health problem of increasing worldwide prevalence related to many reproductive problems such as infertility, ovulation dysfunction, preterm delivery, fetal growth disorders, etc. The mechanisms linking obesity to these pathologies are not fully understood. Cafeteria diet (CAF) is the animal model used for the study of obesity that more closely reflects western diet habits. Previously we described that CAF induces obesity associated to hyperglycemia, reduced ovarian reserve, presence of follicular cysts and ovulatory impairments. The aim of the present study was to contribute in the understanding of the physiological mechanisms altered as consequence of obesity. For that purpose, female Wistar rats were fed ad libitum with a standard diet (control group) or CAF (Obese group). We found that CAF fed-rats developed obesity, glucose intolerance and insulin resistance. Ovaries from obese rats showed decreased glucose uptake and became insulin resistant, showing decreased ovarian expression of glucotransporter type 4 and insulin receptor gene expression respect to controls. These animals showed an increased follicular nitric oxyde synthase expression that may be responsible for the ovulatory disruptions and for inflammation, a common feature in obesity. Obese rats resulted subfertile and their pups were macrosomic. We conclude that obesity alters the systemic and the ovarian glucidic homeostasis impairing the reproductive outcome. Since macrosomia is a risk factor for metabolic and obstetric disorders in adult life, we suggest that obesity is impacting not only on health and reproduction but it is also impacting on health and reproduction of the offspring.  相似文献   

8.
Spaceflight and its bed rest analog impair thermoregulatory responses, including elevated core temperature observed at rest and during exercise. Natural air flow has been found to increase cold sensation significantly compared to artificial constant air flow (CAF). The present study tested the hypothesis that simulated natural air flow (SNAF) ventilation would ameliorate impaired thermoregulatory function to a greater extent than CAF under simulated microgravity conditions. Seven healthy males underwent 30 days of −6° head-down bed rest (HDBR). During pre-HDBR and the day 29 of HDBR (HDBR 29), the subjects were exposed to three air flow patterns at 23 °C while in a supine posture: a still air flow control (CON), CAF, and SNAF. The mean air velocity of the latter two patterns was 0.2 m/s. Subjective perception of the thermal environment was recorded by thermal sensation vote (TSV), and rectal temperature (Tre), skin temperature (Tsk), and cutaneous vascular conductance (CVC) were also measured during the sessions. Tre was significantly elevated after 29 days of HDBR and decreased to a greater extent in SNAF than in CAF on HDBR 29. However, there was no significant difference between Tre in SNAF on HDBR 29 and that in CON on pre-HDBR. Mean Tsk, CVC, and TSV in SNAF were also significantly lower than those in CAF on HDBR 29. Moreover, TSV was close to ‘neutral’ under SNAF on HDBR 29. These data indicate that simulated natural air movement might be more effective than constant air movement at preserving core temperature at a thermoneutral ambient temperature during HDBR.  相似文献   

9.
Triacylglycerols (TG) in milk derive from different sources, and their composition may be influenced by both maternal diet and obesity. We used two rat models to ascertain potential changes in TG composition in milk associated to maternal intake of an obesogenic diet during lactation and to distinguish them from the effects attributable to maternal adiposity. Milk samples were obtained from dams fed a cafeteria diet during lactation (CAF) and from dams made obese by cafeteria diet feeding, with dietary normalization before gestation (PCaf). Levels of specific TG species in milk collected at different time points of lactation were determined by shotgun lipidomics. CAF and PCaf dams presented a greater adiposity than their respective controls. The principal component analysis of TG peaks showed a clear separation between milk from CAF dams and milk from control and Pcaf dams, already evident at 5 days of lactation. Milk from CAF dams was enriched with TG species with greater number of carbons and double bonds and reduced in TG with lower number of carbons. TG composition of milk from Pcaf dams was similar to controls, although specific differences were observed at day 5 of lactation. Thus, the intake of a cafeteria diet during lactation, rather than maternal adiposity, alters milk composition. This effect is avoided with dietary normalization before gestation, although the remaining fat reserves may also influence TG composition at initial stages of lactation. Therefore, normalization of maternal diet prior to pregnancy should be considered as a strategy for achieving optimal milk composition.  相似文献   

10.
11.
Disruption of circadian regulation was recently shown to cause diabetes and metabolic disease. We have previously demonstrated that retinal lipid metabolism contributed to the development of diabetic retinopathy. The goal of this study was to determine the effect of diabetes on circadian regulation of clock genes and lipid metabolism genes in the retina and retinal endothelial cells (REC). Diabetes had a pronounced inhibitory effect on the negative clock arm with lower amplitude of the period (per) 1 in the retina; lower amplitude and a phase shift of per2 in the liver; and a loss of cryptochrome (cry) 2 rhythmic pattern in suprachiasmatic nucleus (SCN). The positive clock arm was increased by diabetes with higher amplitude of circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (bmal1) and phase shift in bmal1 rhythmic oscillations in the retina; and higher bmal1 amplitude in the SCN. Peroxisome proliferator-activated receptor (PPAR) α exhibited rhythmic oscillation in retina and liver; PPARγ had lower amplitude in diabetic liver; sterol regulatory element-binding protein (srebp) 1c had higher amplitude in the retina but lower in the liver in STZ- induced diabetic animals. Both of Elongase (Elovl) 2 and Elovl4 had a rhythmic oscillation pattern in the control retina. Diabetic retinas lost Elovl4 rhythmic oscillation and had lower amplitude of Elovl2 oscillations. In line with the in vivo data, circadian expression levels of CLOCK, bmal1 and srebp1c had higher amplitude in rat REC (rREC) isolated from diabetic rats compared with control rats, while PPARγ and Elovl2 had lower amplitude in diabetic rREC. In conclusion, diabetes causes dysregulation of circadian expression of clock genes and the genes controlling lipid metabolism in the retina with potential implications for the development of diabetic retinopathy.  相似文献   

12.
Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may ameliorate the adverse effects observed in offspring following a maternal obesogenic diet but these effects are dependent upon prior maternal nutritional background.  相似文献   

13.
The aim of this study is to determine the effects of early and mid-gestation nutrient restriction on maternal metabolites and foetal growth. Primiparous Angus cows were synchronized and inseminated with semen from one sire. Dietary treatments were: control to gain 1 kg/week (CON) or 0.55% maintenance energy and CP requirements (nutrient restricted; NR). A subset of dams was fed NR (n=8) or CON (n=8) from days 30 to 110 of gestation. Another group was fed CON (n=8), days 30 to 190; NR (n=7), days 30 to 110 followed by CON days 110 to 190; or CON, (n=7) days 30 to 110 followed by NR days 110 to 190. Cows were harvested at days 110 or 190 of gestation, when foetal measurements and samples were collected. Cows that were NR during days 30 to 110 or 110 to 190 of gestation lost significant BW and body condition score (P<0.001), this was associated with reduced plasma glucose during NR (P<0.002). Foetal weights, empty foetal weights, abdominal and thoracic circumferences were all reduced (P<0.03) in day 110 NR animals. Foetal perirenal adipose as a percentage of empty foetal weight was increased (P=0.01) in NR day 110 female foetuses compared with CON foetus. Maternal serum triglycerides at day 110 of gestation were decreased (P<0.05) in NR dams, whereas foetal serum triglycerides were increased (P<0.05) in response to maternal NR. Foetal weights tended to be reduced (P=0.08) in NR/CON and CON/NR v. CON/CON cattle at day 190 of gestation. Empty foetal weights, abdominal and thoracic circumferences were reduced (P⩽0.03) in NR/CON and CON/NR v. CON/CON cattle. Brain weight as a percentage of empty foetal weight was increased (P<0.001) in NR/CON and CON/NR v. CON/CON cattle. Foetal perirenal adipose as a percentage of empty foetal weight was increased (P=0.003) in NR/CON and CON/NR v. CON/CON cattle. Maternal serum triglycerides at day 190 of gestation were decreased (P<0.05) in association with maternal NR. Foetal serum triglycerides at day 190 of gestation were increased (P<0.05) in response to maternal NR during early gestation but decreased by NR in mid gestation compared with CON foetuses. The data show that maternal nutrient restriction during early or mid-gestation cause’s asymmetrical foetal growth restriction, regardless if the restriction is preceded or followed by a period of non-restriction.  相似文献   

14.
The purpose of the present study was to analyze simultaneously the temporal relationship between the changes of circadian rhythms of brown adipose tissue (BAT) thermogenesis and core temperature (Tc) by dual probe telemetric monitoring transmitters and to determine the role of endogenous arginine vasopressin (AVP) in the circadian rhythms of BAT temperature (TBAT) and Tc in male rats. The key observations in this study are: (1) Increase in TBAT commenced approximately 8 min before Tc increases at the start of transition from the light to dark phase. Whereas at the start of transition from the dark to light phase, decrease in TBAT commenced approximately 3 min before Tc decreases. The data show that circadian changes of BAT thermogenesis do indeed play a significant role in the overall maintenance of the circadian rhythm of core temperature. (2) The plasma AVP level was significantly elevated when core temperature decreases during the light phase, suggesting that endogenous AVP is involved in thermoregulatory processes during the light phase. V1a receptor antagonist could elevate core and BAT temperature during the light period, suggesting that endogenous AVP, acting through V1a receptor, could be involved in tonic thermoregulatory processes.V1a receptor antagonist can increase the blood lipid metabolism, suggesting that the mechanism of endogenous AVP in tonic thermoregulatory processes during light period could involve the suppression of lipolysis in BAT and other peripheral tissues. In summary, this study demonstrated that endogenous vasopressin contributes to reduced BAT themogenesis and body temperature in the light phase of the circadian cycle.  相似文献   

15.
The effect of creatine supplementation, alone or in combination with exercise training, on insulin sensitivity, intramyocellular lipid content (IMCL) and fatty acid translocase (FAT)/CD36 content was investigated in rats fed a sucrose-rich cafeteria diet during 12 weeks. Five experimental conditions were CON, receiving normal pellets; CAF, fed the cafeteria diet; CAFTR, fed the cafeteria diet together with exercise training in weeks 8-12 and CAFCR and CAFCRT that were analogous to CAF and CAFTR, respectively, but which received daily 2.5% of creatine monohydrate. During intravenous glucose tolerance test, compared with CON, whole-body glucose tolerance was reduced in CAF and CAFCR but not in CAFTR and CAFCRT. Insulin-stimulated glucose transport in perfused red gastrocnemius muscles was impaired in CAF and CAFCR but not in the trained groups. IMCL content in soleus and extensor digitorum longus muscles was higher in CAF than in CON, but not in CAFTR, CAFCR and CAFCRT. Compared with CON and CAF, FAT/CD36 protein content in m. soleus, was ∼40% lower in CAFCR, CAFTR and CAFCRT. The fraction of fecal fat, as determined in a 3-week post hoc study, was 25% higher in CAFCR than in CON. Moreover, in CAFCR, triglyceride concentration in blood and liver were significantly lower than in CAF. It is concluded that creatine supplementation in rats on a cafeteria diet inhibits IMCL accumulation via inhibition of gastrointestinal lipid absorption together with lower muscle FAT/CD36 content. Furthermore, exercise-induced but not creatine-induced reduction of IMCL is associated with improved insulin action on glucose transport in muscle cells.  相似文献   

16.
A circadian rhythm in serum leptin, measured every 4 h for 24 h, characterizes normal-weight women (N = 14), and women with gynoid (N = 17) or android (N = 26) obesity, peaking around midnight (P < 0.05), but differing by about 3 h between android and gynoid women (P < 0.01). Obesity is associated with a higher MESOR (rhythm-adjusted mean; P < 0.001) and a smaller relative circadian amplitude (P < 0.05). Gynoid obesity is associated with a larger circadian amplitude of cortisol (P < 0.05), whereas android obesity is associated with a larger circadian amplitude and a higher MESOR of insulin (P < 0.05). Understanding putative mechanisms underlying different body fat distribution may lead to improved chronotherapeutic measures.  相似文献   

17.
The mammalian circadian system develops gradually during ontogenesis, and after birth, the system is already set to a phase of the mothers. The role of maternal melatonin in the entrainment of fetal circadian clocks has been suggested, but direct evidence is lacking. In our study, intact or pinealectomized pregnant rats were exposed to constant light (LL) throughout pregnancy to suppress the endogenous melatonin and behavioral rhythms. During the last 5 days of gestation, the rats were injected with melatonin or vehicle or were left untreated. After delivery, daily expression profiles of c‐fos and Avp in the suprachiasmatic nuclei (SCN), and Per1, Per2, Rev‐erbα, and Bmal1 in the liver were measured in 1‐day‐old pups. Due to the LL exposure, no gene expression rhythms were detected in the SCN of untreated pregnant rats or in the SCN and liver of the pups. The administration of melatonin to pregnant rats entrained the pups' gene expression profiles in the SCN, but not in the liver. Melatonin did not affect the maternal behavior during pregnancy. Vehicle injections also synchronized the gene expression in the SCN but not in the liver. Melatonin and vehicle entrained the gene expression profiles to different phases, demonstrating that the effect of melatonin was apparently not due to the treatment procedure per se. The data demonstrate that in pregnant rats with suppressed endogenous melatonin levels, pharmacological doses of melatonin affect the fetal clock in the SCN but not in the liver. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 131–144, 2015  相似文献   

18.
The circadian rhythms in activity, core temperature (Tc), O2 consumption, CO2 production, and respiratory quotient (RQ) were monitored in four captive Chinese pangolins (Manis pentadactyla). The pangolins were strictly nocturnal, never emerging from their nest before 1600 h, and their intermittent activity continued no later than 0230. As is usual in nocturnal mammals, the highest values observed in Tc, O2 consumption, and CO2 production occurred during the night; the lowest values occurred during the day. The magnitude of the variation in Tc, O2 consumption, CO2 production, and RQ averaged 1.2°C, 1.3 ml O2 kg?1 min?1, 1.2 ml CO2 kg?1 min?1, and 0.24, respectively. The circadian pattern in RQ was independent of activity, Tc, and the metabolic parameters and was of a different character than the patterns exhibited in the other variables. RQ remained constant at either a high or low level for long periods (8–10 h) and then increased or decreased relatively rapidly (1–2h) to the other level as in a square wave, whereas the rhythms in the other variables are similar to sine waves. The sharp increase in RQ was followed by a slow decline in Tc, and the sharp decline in RQ was followed by a slow increase in Tc.  相似文献   

19.
20.
Subterranean common mole voles, Ellobius talpinus, were implanted with long-term recording electronic thermometers to obtain hourly body temperature (Tb) data during either the wintertime or summertime. The two individuals tested during the summertime had significant circadian and ultradian rhythms in their Tb. Four of the five mole voles tested during the wintertime lacked rhythmicity in their Tb. The fifth individual lacked circadian rhythms but had ultradian rhythms in its Tb. A loss of circadian rhythms in Tb during deep torpor or hibernation has been reported for a few species of mammals. Inasmuch as the mole voles' wintertime Tb remained at euthermic levels, our results show that a loss of circadian body temperature rhythms in mole voles does not require the low Tb of deep torpor or hibernation. A tentative conclusion, based on these few animals, is that in common mole voles the Tb rhythms may disappear during the wintertime even though their Tb remains high. (Author correspondence: )  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号