Maternal Obesity and Overnutrition Is Associated with Reduced Systemic Progesterone During the Estrous Cycles of Adult Female Offspring and a Marked Increase in Insulin Resistance at Midpregnancy.

2011 ◽  
Vol 85 (Suppl_1) ◽  
pp. 201-201
Author(s):  
Desiree R. Shasa ◽  
Nathan M. Long ◽  
Peter W. Nathanielsz ◽  
Stephen P. Ford
Keyword(s):  
Insulin Resistance ◽  
Adult Female ◽  
Maternal Obesity ◽  
Female Offspring ◽  
Estrous Cycles

Increased incidence of hepatic insulin-sensitizing substance (HISS)-dependent insulin resistance in female rats prenatally exposed to ethanol

2005 ◽  
Vol 83 (4) ◽  
pp. 383-387 ◽  
Author(s):  
Parissa Sadri ◽  
Dallas J Legare ◽  
Shinichiro Takayama ◽  
W Wayne Lautt
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Adult Female ◽  
Adult Male ◽  
Female Offspring ◽  
In Utero ◽  
Ethanol Exposure ◽  
Prenatally Exposed ◽  
Fetal Alcohol ◽  
Rat Offspring

Insulin causes the release of the hepatic insulin-sensitizing substance (HISS) from the liver. Hepatic parasympathetic nerves play a permissive role in the release of HISS. HISS-dependent insulin resistance (HDIR) occurs in the absence of HISS. Fetal ethanol exposure has been shown to cause dose-dependent HDIR in adult male rat offspring. Since female offspring are more severely affected by in utero ethanol toxicity, we hypothesized that fetal alcohol exposure causes higher incidence and more severe HDIR in adult female offspring. Adult female rat offspring prenatally exposed to different concentrations of ethanol (0%, 15%, and 20%) were tested for insulin sensitivity using the rapid insulin sensitivity test (RIST). The RIST index was significantly reduced in the 15% (134.1 ± 16.1 mg/kg) and the 20% (98.7 ± 9.7 mg/kg) group compared with the 0% (220.9 ± 27.6 mg/kg) group. Administration of atropine produced significant additional HDIR in the 15% group (82.9 ± 14.5 mg/kg) but not the 20% group (83.8 ± 20.5 mg/kg) indicating complete HDIR had been produced in this group, contrary to the adult male offspring in a previous study. The results are consistent with the hypothesis that adult-female offspring are more severely affected by in utero ethanol exposure compared with adult-male offspring.Key words: fetal, alcohol, insulin resistance, gender, HISS, teratology, diabetes.

scholarly journals Maternal High-Fat Diet During Pre-Conception and Gestation Predisposes Adult Female Offspring to Metabolic Dysfunction in Mice

2022 ◽  
Vol 12 ◽  
Author(s):  
Brian Akhaphong ◽  
Brigid Gregg ◽  
Doga Kumusoglu ◽  
Seokwon Jo ◽  
Kanakadurga Singer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Adult Female ◽  
High Fat Diet ◽  
Female Offspring ◽  
Cell Fraction ◽  
Adult Offspring ◽  
High Fat ◽  
Normal Chow

The risk of obesity in adulthood is subject to programming in the womb. Maternal obesity contributes to programming of obesity and metabolic disease risk in the adult offspring. With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of maternal high-fat diet (HFD) during pregnancy on offspring’s metabolic heath trajectory. In the present study, we determined the long-term metabolic outcomes on adult male and female offspring of dams fed with HFD during pregnancy. C57BL/6J dams were fed either Ctrl or 60% Kcal HFD for 4 weeks before and throughout pregnancy, and we tested glucose homeostasis in the adult offspring. Both Ctrl and HFD-dams displayed increased weight during pregnancy, but HFD-dams gained more weight than Ctrl-dams. Litter size and offspring birthweight were not different between HFD-dams or Ctrl-dams. A significant reduction in random blood glucose was evident in newborns from HFD-dams compared to Ctrl-dams. Islet morphology and alpha-cell fraction were normal but a reduction in beta-cell fraction was observed in newborns from HFD-dams compared to Ctrl-dams. During adulthood, male offspring of HFD-dams displayed comparable glucose tolerance under normal chow. Male offspring re-challenged with HFD displayed glucose intolerance transiently. Adult female offspring of HFD-dams demonstrated normal glucose tolerance but displayed increased insulin resistance relative to controls under normal chow diet. Moreover, adult female offspring of HFD-dams displayed increased insulin secretion in response to high-glucose treatment, but beta-cell mass were comparable between groups. Together, these data show that maternal HFD at pre-conception and during gestation predisposes the female offspring to insulin resistance in adulthood.

scholarly journals Effects of exogenous adiponectin supplementation in early pregnant PCOS mice on the metabolic syndrome of adult female offspring

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Meng Zuo ◽  
Guotao Liao ◽  
Wenqian Zhang ◽  
Dan Xu ◽  
Juan Lu ◽  
...  
Keyword(s):  
Adult Female ◽  
Early Pregnancy ◽  
Testosterone Level ◽  
Metabolic Disorders ◽  
Serum Testosterone ◽  
Female Offspring ◽  
Metabolic Phenotype ◽  
Serum Testosterone Level ◽  
The Metabolic Syndrome ◽  
Pcos Group

Abstract Objective PCOS is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities. At present, PCOS has been confirmed to have a certain genetic background. Compared with healthy women, the vast majority of PCOS patients have hyperandrogenemia, and this excessive androgen exposure during pregnancy may affect the development of female fetuses. The aim of the current study was to investigate the effect of adiponectin intervention during early pregnancy of obese mice with PCOS on the metabolic phenotype of adult female offspring. Methods After the PCOS model was established, C57BL/6J mice were divided into maternal-control, maternal-PCOS, and maternal-PCOS + APN groups. DHEA-induced PCOS mice were supplemented with adiponectin (10 mg/kg/day) in the early pregnancy in order to eliminate adverse hormone exposure and then traced for endocrine indicators in their adult female offspring, which were observed for metabolism syndrome or endocrine disturbance and exhibited the main effects of APN. To further explore the underlying mechanism, the relative expressions of phosphorylated AMPK, PI3K, and Akt were detected in the ovaries of offspring mice. Results The serum testosterone level of the maternal-PCOS + APN group in early pregnancy was significantly lower than that of the maternal-PCOS group (p < 0.01). The serum testosterone level in the offspring-PCOS + APN group was significantly lower than in the offspring-PCOS group (p <0.05), the diestrus time characterized by massive granulocyte aggregation in the estrus cycle was significantly shorter than in the offspring-PCOS group (p<0.05), and the phenotypes of PCOS-like reproductive disorders and metabolic disorders, such as obesity, insulin resistance, impaired glucose tolerance, and hyperlipidemia, were also significantly improved in the offspring-PCOS + APN group (p < 0.05). Compared with the control group, the expression levels of phosphorylated AMPK, PI3K, and Akt in the offspring-PCOS group were significantly decreased (p < 0.05), while those in the offspring-PCOS + APN group were significantly increased (p < 0.05). Conclusions APN intervention in early pregnancy significantly reduced the adverse effects of maternal obesity and high androgen levels during pregnancy on female offspring and corrected the PCOS-like endocrine phenotype and metabolic disorders of adult female offspring. This effect may be caused by the activation of the AMPK/PI3K-Akt signaling pathway in PCOS offspring mice.

scholarly journals Prognostic value of different maternal obesity phenotypes in predicting offspring obesity in a family-based cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Jalali-Farahani ◽  
Parisa Amiri ◽  
Bita Lashkari ◽  
Leila Cheraghi ◽  
Farhad Hosseinpanah ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Childhood Obesity ◽  
Maternal Obesity ◽  
Female Offspring ◽  
Normal Weight ◽  
Metabolic Status ◽  
World Health ◽  
Metabolic Phenotype ◽  
Maternal Body Mass Index ◽  
Obesity In Children

Abstract Background Parental weight is studied as an important determinant of childhood obesity; however, obesity-related metabolic abnormalities have been less considered as determinants of childhood obesity. This study aimed to investigate the association between maternal obesity phenotypes and incidence of obesity in their offspring. Methods This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study. A total of 2151 non-obese children who had complete parental information were followed for incidence of obesity over a mean of 148.7 ± 34.7 months. Obesity in children was defined using the World Health Organization criteria. Maternal body mass index (BMI) was classified into three categories: normal weight, overweight and obese. Dysmetabolic status was considered as having metabolic syndrome or diabetes. Metabolic syndrome and diabetes were defined according to the Joint Interim Statement and American diabetes association criteria, respectively. Considering maternal BMI categories and metabolic status, six obesity phenotypes were defined as followed: 1) normal weight and normal metabolic status, 2) overweight and normal metabolic status, 3) obese and normal metabolic status, 4) normal weight and dysmetabolic status, 5) overweight and dysmetabolic status, and 6) obese and dysmetabolic status. The association between maternal obesity phenotypes and incidence of obesity in children was studied using Cox proportional regression hazard model. Results In male offspring, the risk of incidence of obesity significantly increased in those with maternal obesity phenotypes including overweight/normal metabolic: 1.75(95% CI: 1.10–2.79), obese/normal metabolic: 2.60(95%CI: 1.51–4.48), overweight/dysmetabolic: 2.34(95%CI: 1.35–4.03) and obese/dysmetabolic: 3.21(95%CI: 1.94–5.03) compared to the normal weight/normal metabolic phenotype. Similarly, in girls, the risk of incidence of obesity significantly increased in offspring with maternal obesity phenotypes including overweight/normal metabolic: 2.39(95%CI: 1.46–3.90), obese/normal metabolic: 3.55(95%CI: 1.94–6.46), overweight/dysmetabolic: 1.92(95%CI: 1.04–3.52) and obese/dysmetabolic: 3.89(95%CI: 2.28–6.64) compared to normal weight/normal metabolic phenotype. However, maternal normal weight/dysmetabolic phenotype did not significantly change the risk of obesity in both male and female offspring. Conclusion Except for normal weight/dysmetabolic phenotype, all maternal obesity phenotypes had significant prognostic values for incidence of offspring obesity with the highest risk for obese/dysmetabolic phenotype. This study provides valuable findings for identifying the first line target groups for planning interventions to prevent childhood obesity.

scholarly journals Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice

2013 ◽  
Vol 304 (12) ◽  
pp. E1321-E1330 ◽  
Author(s):  
Kazunari Nohara ◽  
Rizwana S. Waraich ◽  
Suhuan Liu ◽  
Mathieu Ferron ◽  
Aurélie Waget ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
Adult Female ◽  
Sympathetic Tone ◽  
Visceral Adiposity ◽  
Androgen Excess ◽  
Altered Expression ◽  
Female Mice ◽  
The Impact

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

scholarly journals Female offspring born to obese and insulin-resistant dams are not at increased risk for obesity and metabolic dysfunction during early development

2018 ◽  
Vol 96 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Hanin Aburasayn ◽  
Rami Al Batran ◽  
Keshav Gopal ◽  
Malak Almutairi ◽  
Amina Eshreif ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Female Offspring ◽  
Metabolic Dysfunction ◽  
Insulin Resistant ◽  
The Metabolic Syndrome ◽  
Rate Versus ◽  
Increased Risk ◽  
Study Completion ◽  
Reduced Rate

The percentage of women who are obese at the time of conception or during pregnancy is increasing, with animal and human studies demonstrating that offspring born to obese dams or mothers are at increased risk for obesity and the metabolic syndrome. Our goal was to confirm in an experimental model of metabolic syndrome in the dam, whether the offspring would be at increased risk of obesity. Conversely, we observed that male offspring born to dams with metabolic syndrome had no alterations in their body mass profiles, whereas female offspring born to dams with metabolic syndrome were heavier at weaning, but exhibited no perturbations in energy metabolism. Moreover, they gained weight at a reduced rate versus female offspring born to healthy dams, and thus weighed less at study completion. Hence, our findings suggest that factors other than increased adiposity and insulin resistance during pregnancy are responsible for the increased risk of obesity in children born to obese mothers.

scholarly journals The consequences of obesity and excess weight gain in pregnancy

2011 ◽  
Vol 70 (4) ◽  
pp. 450-456 ◽  
Author(s):  
Jane E. Norman ◽  
Rebecca Reynolds
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Gestational Diabetes ◽  
Pregnant Women ◽  
Postpartum Haemorrhage ◽  
Maternal Obesity ◽  
Adverse Pregnancy Outcome ◽  
Operative Delivery ◽  
Adverse Pregnancy ◽  
In Pregnancy

The prevalence of obesity in pregnancy is rising exponentially; about 15–20% of pregnant women now enter pregnancy with a BMI which would define them as obese. This paper provides a review of the strong links between obesity and adverse pregnancy outcome which operate across a range of pregnancy complications. For example, obesity is associated with an increased risk of maternal mortality, gestational diabetes mellitus, thromboembolism, pre-eclampsia and postpartum haemorrhage. Obesity also complicates operative delivery; it makes operative delivery more difficult, increases complications and paradoxically increases the need for operative delivery. The risk of the majority of these complications is amplified by excess weight gain in pregnancy and increases in proportion to the degree of obesity, for example, women with extreme obesity have OR of 7·89 for gestational diabetes and 3·84 for postpartum haemorrhage compared to their lean counterparts. The consequences of maternal obesity do not stop once the baby is born. Maternal obesity programmes a variety of long-term adverse outcomes, including obesity in the offspring at adulthood. Such an effect is mediated at least in part via high birthweight; a recent study has suggested that the odds of adult obesity are two-fold greater in babies weighing more than 4 kg at birth. The mechanism by which obesity causes adverse pregnancy outcome is uncertain. This paper reviews the emerging evidence that hyperglycaemia and insulin resistance may both play a role: the links between hyperglycaemia in pregnancy and both increased birthweight and insulin resistance have been demonstrated in two large studies. Lastly, we discuss the nature and rationale for possible intervention strategies in obese pregnant women.

Maternal androgen excess reduces placental and fetal weights, increases placental steroidogenesis, and leads to long-term health effects in their female offspring

2012 ◽  
Vol 303 (11) ◽  
pp. E1373-E1385 ◽  
Author(s):  
Miao Sun ◽  
Manuel Maliqueo ◽  
Anna Benrick ◽  
Julia Johansson ◽  
Ruijin Shao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Adult Female ◽  
Late Pregnancy ◽  
Free Testosterone ◽  
Estrogen Receptor Α ◽  
Female Offspring ◽  
Adipocyte Size ◽  
Nonalcoholic Fatty Liver

Here, we tested the hypothesis that excess maternal androgen in late pregnancy reduces placental and fetal growth, increases placental steroidogenesis, and adversely affects glucose and lipid metabolism in adult female offspring. Pregnant Wistar rats were randomly assigned to treatment with testosterone (daily injections of 5 mg of free testosterone from gestational days 16 to 19) or vehicle alone. In experiment 1, fetal and placental weights, circulating maternal testosterone, estradiol, and corticosterone levels, and placental protein expression and distribution of estrogen receptor-α and -β, androgen receptor, and 17β-hydroxysteroid dehydrogenase 2 were determined. In experiment 2, birth weights, postnatal growth rates, circulating testosterone, estradiol, and corticosterone levels, insulin sensitivity, adipocyte size, lipid profiles, and the presence of nonalcoholic fatty liver were assessed in female adult offspring. Treatment with testosterone reduced placental and fetal weights and increased placental expression of all four proteins. The offspring of testosterone-treated dams were born with intrauterine growth restriction; however, at 6 wk of age there was no difference in body weight between the offspring of testosterone- and control-treated rats. At 10–11 wk of age, the offspring of the testosterone-treated dams had less fat mass and smaller adipocyte size than those born to control rats and had no difference in insulin sensitivity. Circulating triglyceride levels were higher in the offspring of testosterone-treated dams, and they developed nonalcoholic fatty liver as adults. We demonstrate for the first time that prenatal testosterone exposure alters placental steroidogenesis and leads to dysregulation of lipid metabolism in their adult female offspring.

Sign in / Sign up

Export Citation Format

Share Document