Association between intrauterine mild hyperglycemia and post-natal high-fat diet with adiponectin and AMPK pathway genes

To investigate the mechanisms of maternal–fetal interactions in the setting of gestational diabetes mellitus. We investigated the long-term effects of intrauterine mild hyperglycemia and a postnatal high-fat diet on the glucose metabolism of adult offspring, and explored the role of adiponectin on hepatic gluconeogenesis. Twenty-one pregnant Wistar rats were randomly divided into an intrauterine hyperglycemia group (group D, n?=?14) and a control group (group C, n?=?7). Offspring were divided into four groups according to intrauterine blood glucose level and post-weaning dietary patterns (high-fat diet groups: DF and CF or normal diet groups: DN and CN, n?=?8 per group). The average birth weights of group D offspring were higher than for group C. In the DF rats, low adiponectin mRNA expression in perirenal and epididymal fat was significantly positively correlated with low hepatic AdipoR1 mRNA expression and significantly correlated with high hepatic PEPCK, G-6-Pase, and PGC-1α mRNA levels. In DF rats, hepatic P-AMPK was cytoplasmically located and its level was decreased; in these rats, hepatic CRTC2 was expressed in the nucleus and its level was significantly increased. Our study shows that the dietary structure of offspring has a large influence on the incidence of abnormal glucose tolerance.     

Review: Adiponectin – The missing link between maternal adiposity,placental transport and fetal growth?

Adiponectin has well-established insulin-sensitizing effects in non-pregnant individuals. Pregnant women who are obese or have gestational diabetes typically have low circulating levels of adiponectin, which is associated with increased fetal growth. Lean women, on the other hand, have high circulating levels of adiponectin. As a result, maternal serum adiponectin is inversely correlated to fetal growth across the full range of birth weights, suggesting that maternal adiponectin may limit fetal growth. In the mother, adiponectin is predicted to promote insulin sensitivity and stimulate glucose uptake in maternal skeletal muscle thereby reducing nutrient availability for placental transfer. Adiponectin prevents insulin-stimulated amino acid uptake in cultured primary human trophoblast cells by modulating insulin receptor substrate phosphorylation. Furthermore, chronic administration of adiponectin to pregnant mice inhibits placental insulin and mammalian target of rapamycin complex 1 (mTORC1) signaling, down-regulates the activity and expression of key placental nutrient transporters and decreases fetal growth. Preliminary findings indicate that adiponectin binds to the adiponectin receptor-2 on the trophoblast cell and activates p38 MAPK and PPAR-α, which inhibits the insulin/IGF-1 signaling pathway. In contrast to maternal adiponectin, recent reports suggest that fetal adiponectin may promote expansion of adipose tissue and stimulate fetal growth. Regulation of placental function by adiponectin constitutes a novel physiological mechanism by which the endocrine functions of maternal adipose tissue influence fetal growth. These findings may help us better understand the factors determining birth weight in normal pregnancies and in pregnancy complications associated with altered maternal adiponectin levels such as obesity and gestational diabetes.     

Detrimental effect of maternal and post-weaning high-fat diet on the reproductive function in the adult female offspring rat: roles of insulin-like growth factor 2 and the ovarian circadian clock

Purpose

We evaluate the impact of maternal and post-weaning high-fat (HF) diet on ovarian follicular population, steroidogenesis, and gene expression with a focus on the circadian clock system and insulin-like growth factor 2 (Igf2) in adult offspring ovaries, and to elucidate whether a maternal and post-weaning diet confers similar risks.

Methods

Virgin Sprague-Dawley rats were fed with normal chow (C) diet or HF diet for 5 weeks before mating, during gestation, and lactation. Female offspring were fed with the C or HF diet from weaning to 6 months of age, resulting in four study groups (n = 6 per group): C/C, C/HF, HF/C, and HF/HF.

Results

Ovaries from offspring exposed to post-weaning HF diet (i.e., the C/HF and HF/HF groups) had a decrease in small follicle numbers, but with similar numbers of antral follicles and corpora lutea. Offspring from HF-fed dams (i.e., the HF/C and HF/HF groups) had increased plasma estradiol concentrations and decreased luteinizing hormone levels at 6 months of age. In addition, Igf2 and each of the circadian rhythm core genes Clock, Per1, Per2, and Per3 were increased in the ovaries of offspring exposed to maternal HF diet (both HF/C and HF/HF groups).

Conclusions

Maternal and post-weaning HF diet programs the reproductive profile of the female offspring in adult life through different manners. Post-weaning HF intake resulted in the reduction of small follicles in adulthood, whereas maternal HF diet had long-term deleterious consequences on female offspring steroidogenesis and coincided with alteration of the upregulation of the imprinted gene Igf2 and changes in ovarian circadian rhythms.

     

Adiponectin Levels in Circulation and Breast Milk and mRNA Expression in Adipose Tissue of Preeclampsia Women

Objective. Physiological insulin resistance occurs in normal pregnancy and is exaggerated in women with preeclampsia (PE). Adiponectin is a hormone with insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties. Reports published on association between adiponectin levels and PE risk have been conflicting. This study sought to better determine the circulating adiponectin levels and its mRNA expression in adipose tissue in women with PE. Methods. This report includes a cross-sectional study at a Chinese clinical research center and meta-analysis. The cross-sectional study included normal pregnancy women (n = 28) and PE women (n = 20) who underwent cesarean operation. Adiponectin concentrations in maternal serum, cord blood, and colostrums were determined by ELISA. Adiponectin mRNA expression levels in adipose tissue were measured by quantitative real-time PCR. Meta-analysis was done on 13 studies, including 302 PE women and 385 normal pregnancy women. Results. In comparison with controls, PE women had higher serum adiponectin concentrations in maternal blood and breast milk, but lower adiponectin concentration in cord blood. Adiponectin mRNA expression in the subcutaneous (Sc) and omental adipose tissues (OM) did not differ between the two groups of women. Meta-analysis confirms that the circulating adiponectin levels were elevated in PE women (p < 0.01). Conclusions. PE women had a higher adiponectin concentration in the maternal blood as well as breast milk but lower adiponectin concentration in umbilical cord blood when compared to women with normal pregnancy. The elevated circulating adiponectin levels in PE women are probably because of a reduced degradation/elimination rather than an increased synthesis of this hormone.     

AMPK/ERK信号通路在脂联素抑制子宫内膜癌细胞增殖中的作用

目的:探讨脂联素对子宫内膜癌细胞增殖的抑制作用及AMPK/ERK信号传导通路的有关机制。方法:以10μg/ml脂联素作用子宫内膜癌Ishikawa3-H-12细胞0～60min,Western blot检测脂联素作用不同时间后细胞AMPK及ERK的磷酸化程度。脂联素作用12,24h后,分别采用RT-PCR和Western blot检测Cyclin D1 mRNA和蛋白水平。脂联素作用48h,MTT法检测细胞增殖。结果:脂联素以时间依赖方式诱导子宫内膜癌细胞AMPK活化,脂联素作用5min后明显活化,并维持至30min(F=22.749,P=0.000),AMPK抑制剂复合物C可明显抑制脂联素诱导的细胞AMPK活化。脂联素以时间依赖模式抑制子宫内膜癌细胞ERK活化,作用5min ERK活化明显受抑制,并维持至少60min(F=13.802,P=0.000),复合物C明显阻断脂联素诱导的细胞ERK活性抑制。脂联素明显抑制Cyclin D1 mRNA转录和蛋白表达(P=0.003,P=0.000),复合物C明显阻断脂联素对细胞Cyclin D1 mRNA转录和蛋白表达的抑制作用(P=0.006,P=0.000)。脂联素明显抑制细胞增殖(P=0.001),复合物C明显阻断脂联素对细胞的抑制作用(P=0.002)。结论:脂联素可能通过AMPK/ERK/Cyclin D1途径抑制子宫内膜癌细胞增殖。     

Adiponectin and glucose levels in women with negative or false positive glucose challenge test

OBJECTIVE: To determine whether there is a correlation between adiponectin levels and glucose levels in women screened for gestational diabetes mellitus by means of a 50-g oral glucose challenge test, and to examine the difference in adiponectin levels between women who tested negative, and those who tested false positive. We further calculated the correlations between adiponectin levels and glucose levels, body mass index, gestational age and maternal age. METHODS: A case control study included 171 mothers with negative or false positive results in the 1-h 50-g glucose challenge test at 24-28 gestational weeks. Serum adiponectin levels were determined by radioimmunoassay at the time of the glucose challenge test. RESULTS: There was a significant difference between women who tested negative at screening, and those who tested false positive with respect to age, prepregnancy body weight and body mass index, and adiponectin levels. Correlation analysis showed adiponectin levels to be negatively correlated to glucose levels (r=-0.193, P=0.011). To examine the association between glucose levels, adiponectin levels and demographic variables, multiple linear regression analysis was carried out. Prepregnancy body mass index and age accounted for 14.6% of the variance in the glucose challenge test. Adiponectin levels did not contribute independently to the variation in glucose levels. A further multiple linear regression analysis was undertaken to investigate the association between adiponectin levels and age, prepregnancy body mass index and glucose levels in the glucose challenge test. In this regression model, prepregnancy body mass index and age explained 12.1% of the variance in adiponectin levels. CONCLUSIONS: In conclusion, our study indicated a negative correlation between adiponectin and glucose levels in women screened for gestational diabetes mellitus by a glucose challenge test. We further found that maternal age and body mass index were independent risk factors for a false positive glucose challenge test. Reduced adiponectin levels in women who tested false positive on the glucose challenge test were dependent on advanced age and higher body mass index.     

Maternal high-fat diets cause insulin resistance through inflammatory changes in fetal adipose tissue

Objectives

Epidemiological and animal studies have shown that maternal obesity predisposes the offspring to obesity and the metabolic syndrome, possibly via late-onset metabolic programming of the fetus. Little is known, however, about the metabolic effect of maternal obesity on the fetus. This study investigated the effect of a maternal high-fat diet (HFD) on fetal growth and glucose metabolism using a diet-induced obesity mouse model.

Study design

Female mice (6 weeks old; C57BL/6N) were fed either a normal chow diet (NCD, 10 kcal% fat) or an HFD (60 kcal% fat) for 4 weeks before mating and throughout pregnancy. At 17 days of gestation, gene expression of inflammatory markers and adipokines in fetal subcutaneous adipose tissue was analyzed by quantitative real-time polymerase chain reaction.

Results

HFD mice were overweight, glucose intolerant and insulin resistant compared with NCD mice of the same gestational age. Although fetal body weight was not significantly different, fetal plasma glucose and insulin levels were higher in the HFD group than the NCD group. Furthermore, examination of fetal subcutaneous adipose tissue in the HFD group revealed hypertrophy with an increase in the levels of cluster of differentiation-68, chemokine receptor-2 and tumor necrosis factor-α mRNA, but a decrease in the level of glucose transporter-4 mRNA.

Conclusion

Maternal HFD causes inflammatory changes in the adipose tissue of offspring.     

Serum adiponectin during pregnancy and postpartum in women with gestational diabetes and normal controls

Aims. To investigate changes in serum adiponectin during pregnancy and postpartum and assess its relationship with insulin resistance as measured by homeostasis model assessment (HOMA-IR).

Methods. Twenty-two normal pregnant women were compared with 22 women diagnosed with gestational diabetes mellitus (GDM). Serum adiponectin levels were measured at the time of the glucose challenge test as well as in the immediate postpartum period and the correlation of adiponectin to HOMA-IR was performed.

Results. Adiponectin was significantly lower in women with GDM than in controls during pregnancy (5381 vs. 8449 ng/dl, p = 0.004), as well as postpartum (3278 vs. 6958 ng/ml, p = 0.002). A significant reduction in adiponectin (3278 vs. 5381 ng/ml, p = 0.002) was observed postpartum in GDM women but not in controls. Using a lower cut-off value of 5253 ng/ml, maternal adiponectin could exclude GDM with a sensitivity of 86.4% and a specificity of 59.1% (area under the curve = 0.752, standard error = 0.77, 95% confidence interval 0.601–0.903, p = 0.004). Adiponectin levels during pregnancy were negatively correlated with HOMA-IR (r = ?0.375, p = 0.012).

Conclusion. GDM is associated with decreased serum adiponectin levels both in pregnancy as well as postpartum. Adiponectin is negatively correlated to HOMA-IR. A reduction in maternal adiponectin after delivery indicates a significant placental contribution to adiponectin production.     

Insulin sensitivity in late gestation and early postpartum period: the role of circulating maternal adipokines

Objective.?Early postpartum period is characterised by a dramatic decrease in insulin resistance and significant metabolic alterations. The aims of this study were to determine the changes in circulating maternal concentrations of total adiponectin, adiponectin multimers, leptin and resistin before and after the delivery and to explore their relationship with insulin sensitivity.

Methods.?Twenty-seven normal pregnant women at term were included in this longitudinal study. Blood samples were taken before and 4 days after elective caesarean section. Total adiponectin, adiponectin multimers, leptin, resistin, glucose, insulin and prolactin were measured in maternal serum. Adiponectin multimers were measured before and after the delivery in eight women.

Results.?(1) The mean maternal serum total adiponectin concentration was significantly higher before than after delivery while the relative distribution of circulating maternal adiponectin multimers did not change after delivery; (2) the median maternal serum concentration of leptin was significantly higher in the antepartum than in the postpartum period; (3) the median maternal serum resistin concentration was comparable before and after delivery; (4) multiple linear regression analysis revealed that antepartum insulin sensitivity was associated with maternal low body mass index, and low glucose concentrations in glucose challenge test, as well as with maternal age and increased leptin concentrations. Postpartum insulin sensitivity was associated with decreased circulating resistin concentrations.

Conclusions.?Despite increase in insulin sensitivity, early postpartum period is characterised by a decrease in maternal circulating total adiponectin and by steady concentrations of resistin and adiponectin multimers compared to the late third trimester.     

脂联素、胰岛素抵抗与子宫内膜癌的发生发展

脂联素(adiponectin)为脂肪组织特异性分泌的一种内源性细胞因子,通过与脂联素受体(AdipoR)结合发挥特异的生物学效应。血清脂联素水平降低与肥胖、胰岛素抵抗(IR)有关,且与IR程度呈正相关。临床研究显示脂联素水平降低与子宫内膜癌发生相关。AdipoR的表达随着临床分期及组织学分级的升高、肌层浸润加重、淋巴结转移而明显下降,且与无进展生存时间及生存率呈负相关。脂联素与AdipoR结合,激活多种信号传导通路的下游,并可与胰岛素信号通路相互作用,抑制细胞增殖,诱导肿瘤细胞凋亡。因此,脂联素水平降低同时存在IR会促进子宫内膜癌发生,是其发病的危险因素。     

Programmed hyperphagia due to reduced anorexigenic mechanisms in intrauterine growth-restricted offspring

Maternal food restriction during pregnancy results in intrauterine growth-restricted (IUGR) newborns with significantly decreased plasma leptin levels. When nursed by ad libitum-fed controls, IUGR offspring exhibit hyperphagia with adult obesity, marked by increased percentage body fat and plasma leptin, suggesting altered anorexigenic pathways. The authors examined leptin signaling pathways and food intake responses to 2 putative anorexic effectors (leptin and sibutramine, a serotonin reuptake inhibitor) in IUGR offspring. From 10 days to term gestation and through lactation, control pregnant rats received ad libitum food, whereas study rats were 50% food restricted. Following birth, litter size was standardized, and all offspring were nursed by control dams. At 3 weeks of age, offspring were weaned to ad libitum laboratory chow. At ages 1 day and 3 weeks, hypothalamic leptin receptor (Ob-Rb) mRNA and total STAT3 protein expression were determined. In addition, phosphorylated STAT3 was measured in 1-day-old offspring administered peripheral leptin. In prepubescent and adult offspring, anorexic effects of leptin and sibutramine were determined. At 1 day of age, IUGR pups showed increased hypothalamic Ob-Rb mRNA and total STAT3 protein expression though reduced leptin activated phosphorylated STAT3. At 3 weeks of age, IUGR offspring had decreased hypothalamic Ob-Rb mRNA expression, although with continued elevated STAT3 protein levels. The IUGR offspring demonstrated resistance to anorexigenic agents, leptin (6 weeks and 6 months), and sibutramine (8 months), as evidenced by less reduction in food intake and less body weight loss than controls. The IUGR offspring demonstrate suppressed leptin-induced STAT3 phosphorylation and impaired anorexigenic response to 2 factors in the central satiety pathway. This reduced anorexigenic function, together with normal or perhaps enhanced orexigenic function, contributes to the development of programmed obesity in IUGR rat offspring.     

Murine aortic reactivity is programmed equally by maternal low protein diet or late gestation dexamethasone.

OBJECTIVE: In rats, maternal low protein diet induces growth restriction, increases fetal glucocorticoid exposure and programs cardiovascular and endocrine dysfunction in adult offspring. We hypothesized that both maternal low protein diet and late gestation dexamethasone program murine offspring to develop hypertension, vascular dysfunction, and glucose intolerance. METHODS: An iso-caloric low protein diet (LP) was provided to dams from E0 to E19. Additional dams received a normal protein diet without (NP) or with either dexamethasone (NP-Dex, 0.1 mg/kg/d sc) or normal saline (NP-NS) from E10 to E18. RESULTS: Offspring of dams given LP weighed less at 10 days than NP offspring, while Dex administration did not alter pup weight. At 4 months, all four groups had similar systolic blood pressures and no detectable differences were evoked by oral L-NAME. Offspring of LP mice had impaired glucose clearance that was directly correlated with their weight at 10 days. Aortic rings from offspring of both LP and NP-Dex exposed dams had impaired vasodilatation to acetylcholine. CONCLUSIONS: These findings demonstrate that both maternal low protein diet and late gestation dexamethasone program murine offspring to develop endothelial dysfunction in the absence of hypertension, while only maternal LP impaired perinatal growth and glucose clearance in adult offspring. Keywords: Acetylcholine; blood pressure; developmental biology; fetal programming     

Adipocytokine expression in placentas from pre-eclamptic and chronic hypertensive patients.

OBJECTIVE: Growing evidence suggests that concentration of the adipocytokines leptin and adiponectin may be affected by risk of hypertension during pregnancy. Leptin and leptin receptor gene expression has been studied in placentas obtained from pre-eclamptic patients, but not in those with chronic high blood pressure (CHBP). Adiponectin receptors remain unstudied in placentas obtained from hypertensive patients. METHODS: Therefore, we investigated relative mRNA expression of selected adipocytokine genes (leptin, leptin receptors (LEPRA, LEPRB, LEPRC, LEPRD) and adiponectin receptors (ADIPOR1, ADIPOR2)) in placental tissues from women with pre-eclampsia (n = 6) or CHBP (n = 8). Placentas from 28 normotensive patients were analyzed as controls. mRNA extracted from biopsies taken from the maternal and fetal sides of the placenta was investigated using real-time polymerase chain reaction. RESULTS: Compared with controls, significant increases in leptin mRNA expression were seen in placentas from pre-eclamptic patients on the maternal (p = 0.01) and fetal (p = 0.02) sides, and in placentas from CHBP mothers on the fetal side (p = 0.001). Maternal-side tissue from CHBP patients was not significantly different from that of controls (p = 0.08), but this might be due to the small sample size. No significant differences were seen in mRNA expression for most of the adipocytokine receptors tested for hypertensive cases compared with controls. However, there was a decrease in LEPRC (pre-eclamptic, maternal side, p = 0.03) and LEPRD (pre-eclamptic, maternal side, p = 0.01; CHBP, fetal side, p = 0.009) in case-control analysis. CONCLUSIONS: This pilot study shows that increases seen in leptin expression in placentas from hypertensive mothers might be a consequence of defects in placentation associated with this disease, and motivates further region-specific adipocytokine gene expression analysis across this organ.     

胰岛素抵抗及子宫内膜增殖大鼠模型中脂肪因子和PI3K/AKT信号通路相关蛋白的表达

目的:观察有胰岛素抵抗及子宫内膜增殖大鼠模型中血浆脂联素(Adipo)等脂肪因子的水平,检测Adipo和脂联素受体(AdipoR)在大鼠子宫组织中的表达,并探讨其分子生物学机制。方法:选取8周龄Sprague-Dawley(SD)大鼠45只(每组9只),分别给予普通饮食(StD组)和高脂饮食(HFD组)40周。将StD组分为对照C组(普通饮食+假去势手术+对照溶剂)、NO组(普通饮食+去势手术+对照溶剂)、NE组(普通饮食+去势手术+17β-雌二醇灌胃),HFD组分为FO组(高脂饮食+去势手术+对照溶剂)和FE组(高脂饮食+去势手术+17β-雌二醇灌胃)。应用酶联免疫吸附(ELISA)检测小鼠血浆中脂肪因子水平,实时荧光定量PCR、Western Blotting和免疫组化检测子宫内膜中脂肪因子的水平,免疫组化检测子宫内膜中PTEN、AMPK和PI3K/AKT信号通路相关蛋白的表达。结果:①与NE组大鼠相比,FE组大鼠子宫腔上皮细胞和腺上皮细胞的高度、肌层的厚度显著增加(P<0.05)。②与对照C组相比,子宫内膜增生组(NE组和FE组)大鼠血浆Adipo水平显著降低(P<0.05),FO组大鼠血浆Adipo显著升高(P<0.05)。③在雌激素的作用下(NE组和FE组)子宫组织中Adipo mRNA的表达增多:与NO组大鼠相比,NE组大鼠子宫组织中Adipo mRNA水平显著升高(P<0.05);与FO组大鼠相比,FE组大鼠Adipo mRNA水平也显著升高(P<0.05)。大鼠子宫中AdipoR1 mRNA和AdipoR2 mRNA水平在各组之间差异无统计学意义(P>0.05)。与对照C组相比,FE组大鼠子宫组织中Adipo蛋白的表达明显降低(P<0.05)。④FE组子宫PTEN和p-AMPK蛋白的表达显著低于对照C组(P<0.05),PI3Kp85α、p-AKT蛋白表达显著高于对照C组(P<0.05)。结论:长期高脂饮食诱导大鼠的胰岛素抵抗可协同17β-雌二醇刺激子宫内膜增殖;胰岛素抵抗和雌激素影响血浆Adipo的水平;胰岛素抵抗和雌激素的协同作用使大鼠子宫内膜PTEN的表达降低、AMPK通路可能被抑制、PI3K/AKT信号通路可能被激活。     

Murine aortic reactivity is programmed equally by maternal low protein diet or late gestation dexamethasone

Objective. In rats, maternal low protein diet induces growth restriction, increases fetal glucocorticoid exposure and programs cardiovascular and endocrine dysfunction in adult offspring. We hypothesized that both maternal low protein diet and late gestation dexamethasone program murine offspring to develop hypertension, vascular dysfunction, and glucose intolerance.

Methods. An iso-caloric low protein diet (LP) was provided to dams from E0 to E19. Additional dams received a normal protein diet without (NP) or with either dexamethasone (NP-Dex, 0.1 mg/kg/d sc) or normal saline (NP-NS) from E10 to E18.

Results. Offspring of dams given LP weighed less at 10 days than NP offspring, while Dex administration did not alter pup weight. At 4 months, all four groups had similar systolic blood pressures and no detectable differences were evoked by oral L-NAME. Offspring of LP mice had impaired glucose clearance that was directly correlated with their weight at 10 days. Aortic rings from offspring of both LP and NP-Dex exposed dams had impaired vasodilatation to acetylcholine.

Conclusions. These findings demonstrate that both maternal low protein diet and late gestation dexamethasone program murine offspring to develop endothelial dysfunction in the absence of hypertension, while only maternal LP impaired perinatal growth and glucose clearance in adult offspring.     

Decreased plasma adiponectin concentrations in women with gestational diabetes mellitus

OBJECTIVE: Adiponectin is an adipocyte-specific protein that has been found to be associated with insulin sensitivity and obesity. Because gestational diabetes mellitus is associated with obesity and decreased insulin sensitivity, we have analyzed plasma adiponectin levels in women with gestational diabetes mellitus. STUDY DESIGN: Twenty women with gestational diabetes mellitus and 21 unaffected women were included in the study. Plasma adiponectin levels were analyzed with the use of enzyme-linked immunosorbent assay. RESULTS: Women with gestational diabetes mellitus were significantly older (34.3 years vs 29.4 years; P < .001) than unaffected women. Adiponectin plasma levels were significantly lower in women with gestational diabetes mellitus when compared with women without gestational diabetes mellitus (5827 +/- 1988 ng/mL vs 8085 +/- 3816 ng/mL; P = .02). Adiponectin plasma levels were correlated negatively with plasma glucose concentrations of the oral glucose tolerance test ( r > -0.38; P < .04) and correlated positively with gestational age ( r = 0.36; P = .03). CONCLUSION: Our data show that decreased plasma adiponectin levels were found in women with gestational diabetes mellitus compared with unaffected women.     

Correlations between umbilical and maternal serum adiponectin levels and neonatal birthweights

OBJECTIVE: To measure adiponectin levels in maternal serum and umbilical cord serum at delivery, and examine whether or not there are correlations between adiponectin levels and neonatal birthweights, maternal body weights and body mass indexes. STUDY DESIGN: The study included 84 healthy mothers who had given birth to healthy neonates. Adiponectin levels in maternal serum and umbilical cord serum were determined by radioimmunoassay and compared. RESULTS: The ranges of adiponectin levels for umbilical cord serum and maternal serum were 22.7-78.4 microg/ml and 4.0-43.3 microg/ml, respectively. Umbilical serum adiponectin levels (46.9 +/- 1.2 microg/ml) were significantly higher than maternal serum adiponectin levels (16.1 +/- 0.8 micro g/ml) (p < 0.001). No correlation was found between the adiponectin levels in maternal serum and those in umbilical cord serum (r = 0.158, p = 0.151). Umbilical serum adiponectin levels were significantly correlated with both neonatal birthweights (r = 0.454, p < 0.001) and gestational ages at birth (r = 0.295, p = 0.006), but not with maternal serum adiponectin levels. Maternal serum adiponectin levels were only negatively correlated to maternal weights and body mass index at delivery (r = 0.288, p = 0.008; r = 0.372, p < 0.001). CONCLUSION: The levels of adiponectin were higher in umbilical cord serum than in maternal serum. Moreover, the adiponectin levels in umbilical cord serum were found to correlate positively with neonatal birthweights. Therefore, fetal adiponectin, not maternal serum adiponectin, may be involved in fetal development during late pregnancy.     

多囊卵巢综合征患者血清脂联素水平及与胰岛素抵抗相关性的研究

目的:检测多囊卵巢综合征(PCOS)患者血清脂联素(APN)水平,探讨APN与胰岛素抵抗(IR)的相关性。方法:研究对象于月经周期第3~5天行75g糖耐量实验(OGTT实验),分别测定0h、1h、2h的血糖(FPG、PG1h、PG2h)、胰岛素(FINS、INS1h、INS2h)和脂联素(FAPN、APN1h、APN2h)。PCOS患者给予达英-353个周期联合二甲双胍治疗3个月后复查上述指标,比较治疗前后的变化。结果:(1)PCOS组与对照组均表现为肥胖组APN水平低于非肥胖组,且PCOS组中肥胖组与非肥胖组的APN水平均低于对照组(P<0.05);(2)PCOS组中肥胖组与非肥胖组的FINS、INS1h、INS2h、AUCins及HOMA-IR均高于对照组,且肥胖PCOS组高于非肥胖PCOS组(P<0.05);(3)PCOS组经二甲双胍联合达英-35治疗后FINS、INS1h、INS2h、AUCins、HOMA-IR均降低(P<0.05),而APN水平明显升高;(4)相关性分析表明,PCOS患者APN水平与FINS、INS1h、INS2h、FPG、AUCins、HOMA-IR和BMI均呈负相关。多元逐步回归分析显示,APN与FINS、HOMA-IR的相关性最显著。结论:PCOS患者APN水平显著降低与IR密切相关。     

Downregulation of adiponectin system in granulosa cells and low levels of HMW adiponectin in PCOS

Purpose

The purpose of the study was to investigate changes in adiponectin system expression in granulosa cells (GCs) and high molecular weight adiponectin levels in serum and follicular fluid (FF) of 40 women with polycystic ovary syndrome (PCOS) compared to those in 40 women with normal ovary function.

Methods

Adiponectin (Adipo), adiponectin receptor 1 (AdipoR1), and adiponectin receptor 2 (AdipoR2) messenger RNA (mRNA) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). High molecular weight (HMW) adiponectin protein concentration was evaluated by ELISA method. Data were analyzed using Student’s t test and one-way ANOVA in SPSS 21 software. At oocyte retrieval, FF was aspirated and GCs were obtained from a pooled collection of FF per each patient.

Results

PCR results showed expression of adiponectin, AdipoR1, AdipoR2, follicle-stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) in GCs. After controlling body mass index (BMI) values, qRT-PCR demonstrated a decreased expression of adiponectin system in GCs of PCOS patients compared to those in controls (p = 0.001). There was a strong positive correlation among AdipoR1 and AdipoR2 expression and also among FSH and LH receptor expression. (Both r = 0.8, p = 0.001). There were low levels of high molecular weight adiponectin in the serum of PCOS patients with controlled ovarian hyperstimulation (30.19 ± 4.3 ng/ml) compared to the controls (48.47 ± 5.9 ng/ml) and in the FF of PCOS patients with controlled ovarian hyperstimulation (7.86 ± 1.44 ng/ml) compared to the controls (14.22 ± 2.01 ng/ml; p = 0.02).

Conclusions

Lower expression of adiponectin and its receptors in GCs might be an important manifestation in gonadotropin-stimulated PCOS patients which could influence the physiologic adiponectin roles such as interaction with insulin and LH in induction of GC gene expression.