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Adiponectin and maternal obesity increased fetal blood FFA. Fetuses were generated using the same breeding scheme 1 (A and B) or 2 (C), as in Supplementary Fig. 1. For the maternal obesity study (A and B), dams were fed with HF or LF diet for 6 weeks before and during gestation. Regular chow was provided to the dams described in C. Fetal blood was collected by heart puncture. Maternal obesity increased blood FFA levels of fetuses from WT dams but not in fetuses from Adipoq−/− dams (A). Maternal HF feeding did not alter fetal TG levels of both WT and Adipoq−/− dams (B). Blood FFA concentrations of Adipoq−/+ fetuses were significantly higher than that of Adipoq−/− fetuses (C). *P < 0.05 vs. F-LF diet or F-HF diet fetuses of WT dams. F-HFD, fetuses from HF diet–fed dams; F-LFD, fetus from LF diet–fed dams. n = 21–24.
Source publication
Maternal obesity increases offspring birth weight and susceptibility to obesity. Adiponectin is an adipocyte-secreted hormone with a prominent function in maintaining energy homeostasis. In contrast to adults, neonatal blood adiponectin levels are positively correlated with anthropometric parameters of adiposity. This study was designed to investig...
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Citations
... Concerning adiponectin signaling, numerous studies have been carried out to establish its role during pregnancy, even though circulating adiponectin in pregnant women appears to be compartmentalized between the maternal and fetal systems [99]. In particular, placental signaling by AdipoR1, associated with PPAR-α activation, has been shown to benefit fetal growth [100,101]. With regard to adiponectin receptor agonists, AdipoRon transfer across the placenta has not been formally verified. ...
Zika virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique characteristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This challenges the search for safe active molecules that can protect pregnant women and their fetuses. In this context, and in the absence of any existing treatment, it seemed worthwhile to test whether the known cytoprotective properties of adiponectin and its pharmacological analog, AdipoRon, could influence the outcome of ZIKV infection. We showed that both AdipoRon and adiponectin could significantly reduce the in vitro infection of A549 epithelial cells, a well-known cell model for flavivirus infection studies. This effect was particularly observed when a pre-treatment was carried out. Conversely, ZIKV revealed an ability to downregulate adiponectin receptor expression and thereby limit adiponectin signaling.
... We filtered out 3 genes (ITGB4, TXNRD2, RRM2B) as potential causative genes for SGA and 1 gene (ADI-POQ) as potential causative gene for SGA with poor prognosis. The ADIPOQ gene encodes adiponectin that circulates in the plasma and is involved with metabolic and hormonal processes, adiponectin gene knockout mice had known to suffer developmental failure phenotypes such as abnormal growth, increased energy expenditure, decreased fat content, and lower body weight [56,57]. Thus abnormalities in this gene lead to postnatal developmental delay, which is consistent with our finding that it is a potential causative gene for SGA with poor prognosis. ...
Background
In China, ~1,072,100 small for gestational age (SGA) births occur annually. These SGA newborns are a high-risk population of developmental delay. Our study aimed to evaluate the genetic profile of SGA newborns in the newborn intensive care unit (NICU) and establish a prognosis prediction model by combining clinical and genetic factors.
Methods
A cohort of 723 SGA and 1317 appropriate for gestational age (AGA) newborns were recruited between June 2018 and June 2020. Clinical exome sequencing was performed for each newborn. The gene-based rare-variant collapsing analyses and the gene burden test were applied to identify the risk genes for SGA and SGA with poor prognosis. The Gradient Boosting Machine framework was used to generate two models to predict the prognosis of SGA. The performance of two models were validated with an independent cohort of 115 SGA newborns without genetic diagnosis from July 2020 to April 2022. All newborns in this study were recruited through the China Neonatal Genomes Project (CNGP) and were hospitalized in NICU, Children’s Hospital of Fudan University, Shanghai, China.
Results
Among the 723 SGA newborns, 88(12.2%) received genetic diagnosis, including 42(47.7%) with monogenic diseases and 46(52.3%) with chromosomal abnormalities. SGA with genetic diagnosis showed higher rates in severe SGA(54.5% vs. 41.9%, P=0.0025) than SGA without genetic diagnosis. SGA with chromosomal abnormalities showed higher incidences of physical and neurodevelopmental delay compared to those with monogenic diseases (45.7% vs. 19.0%, P=0.012). We filtered out 3 genes (ITGB4, TXNRD2, RRM2B) as potential causative genes for SGA and 1 gene (ADIPOQ) as potential causative gene for SGA with poor prognosis. The model integrating clinical and genetic factors demonstrated a higher area under the receiver operating characteristic curve (AUC) over the model based solely on clinical factors in both the SGA-model generation dataset (AUC=0.9[95% confidence interval 0.84–0.96] vs. AUC=0.74 [0.64–0.84]; P=0.00196) and the independent SGA-validation dataset (AUC=0.76 [0.6–0.93] vs. AUC=0.53[0.29–0.76]; P=0.0117).
Conclusion
SGA newborns in NICU presented with roughly equal proportions of monogenic and chromosomal abnormalities. Chromosomal disorders were associated with poorer prognosis. The rare-variant collapsing analyses studies have the ability to identify potential causative factors associated with growth and development. The SGA prognosis prediction model integrating genetic and clinical factors outperformed that relying solely on clinical factors. The application of genetic sequencing in hospitalized SGA newborns may improve early genetic diagnosis and prognosis prediction.
... This study revealed that serum adiponectin levels were not different between the successful and unsuccessful subjects in all three phases of the IVF/ICSI treatment and they did not change across the various phases of IVF/ICSI treatment in either group. These findings were in accordance with previous publications revealing that adiponectinnull mice were not related to a diminished reproductive ability [20][21][22]. We postulated that adiponectin might not exert beneficial effects on the outcome of IVF/ICSI treatment. ...
This study investigated the roles of adiponectin in IVF treatment during Phase I (the basal stage before gonadotropin administration), Phase II (approximately 8 days after gonadotropin administration), and Phase III (on the ovum pick-up day), as well as the effects of adiponectin on CYP19A1 and the FSH receptor (FSHR) mRNA expression in a human granulosa-like tumor cell line (KGN). In human subjects (a longitudinal study, n = 30), blood samples were collected in all phases, while follicular fluid (FF) was only collected in Phase III. The participants were classified into successful and unsuccessful groups based on the determination of fetal heartbeats. KGN cells were treated with adiponectin/FSH/IGF-1 (an experimental study, n = 3). There was no difference in the adiponectin levels between successful and unsuccessful pregnancies in the FF (Phase III) and in serum (all phases), as well as among the three phases in both groups. Serum FSH (Phase I) was positively associated with serum adiponectin in the unsuccessful group, but it had a negative association in the successful group (all phases). Serum adiponectin and serum FSH (Phase I) were positively correlated in the unsuccessful group, whereas they were negatively correlated (all phases) in the successful group. The serum adiponectin levels (Phase III) were significantly higher than in the FF in unsuccessful pregnancies, but there was no difference in successful pregnancies. FF adiponectin concentrations were negatively correlated with serum LH in successful subjects. In KGN cells, adiponectin had no influence on CYP19A1 and FSHR mRNA expression. High adiponectin levels in serum compared to FF (Phase III) in unsuccessful subjects might negatively impact IVF treatment.
... Importantly, diet-induced obesity is associated with lipid burden in adipose tissue, as well as in non-adipose tissue. The increased fat deposition was observed in the liver and eventually leads to weight gain in the obese animal model [36,[56][57][58]. Our data reveal a similar trend of reduction of liver weight in HFD-induced rats after administration of the Mei-Gin formula. ...
Background:
To investigate the potential anti-obesity properties of an innovative functional formula (called the Mei-Gin formula: MGF) consisting of bainiku-ekisu, Prunus mume (70% ethanol extract), black garlic (water extract), and Mesona procumbens Hemsl. (40% ethanol extract) for reducing lipid accumulation in 3T3-L1 adipocytes in vitro and obese rats in vivo.
Material and methods:
The prevention and regression of high-fat diet (HFD)-induced obesity by the intervention of Japan Mei-Gin, MGF-3 and -7, and positive health supplement powder were investigated in male Wistar rats. The anti-obesity effects of MGF-3 and -7 in rats with HFD-induced obesity were examined by analyzing the role of visceral and subcutaneous adipose tissue in the development of obesity.
Results:
The results indicated that MGF-1-7 significantly suppressed lipid accumulation and cell differentiation through the down-regulation of GPDH activity, as a key regulator in the synthesis of triglycerides. Additionally, MGF-3 and MGF-7 exhibited a greater inhibitory effect on adipogenesis in 3T3-L1 adipocytes. The high-fat diet increased body weight, liver weight, and total body fat (visceral and subcutaneous fat) in obese rats, while these alterations were effectively improved by the administration of MGF-3 and -7, especially MGF-7.
Conclusion:
This study highlights the role of the Mei-Gin formula, particularly MGF-7, in anti-obesity action, which has the potential to be used as a therapeutic agent for the prevention or treatment of obesity.
... While maternal adiponectin decreases throughout gestation, fetal adiponectin increases, promoting fat deposition and fetal growth [177]. Fetal adiponectin is postulated to have the opposite effect of circulating adiponectin in adults. ...
... Consistent with this, fetal adiponectin and maternal blood glucose levels are inversely correlated in the second trimester [12,37]. In rodent studies, fetal adiponectin was found to promote adiposity [177]. Administration of full-length adiponectin increased litter size and decreased neonatal size in mice [173]. ...
... In contrast to maternal adiponectin, fetal adiponectin serves to promote fetal growth and adipose deposition, possibly by increasing fetal insulin resistance [36]. Fetal fat deposition was impaired in fetuses from adiponectin-null dams but not in heterozygous mice [177]. There is also an inverse relationship between maternal adiponectin and fetal growth, with low circulating adiponectin associated with LGA infants [181]. ...
Pregnancy involves a range of metabolic adaptations to supply adequate energy for fetal growth and development. Gestational diabetes (GDM) is defined as hyperglycemia with first onset during pregnancy. GDM is a recognized risk factor for both pregnancy complications and long-term maternal and offspring risk of cardiometabolic disease development. While pregnancy changes maternal metabolism, GDM can be viewed as a maladaptation by maternal systems to pregnancy, which may include mechanisms such as insufficient insulin secretion, dysregulated hepatic glucose output, mitochondrial dysfunction and lipotoxicity. Adiponectin is an adipose-tissue-derived adipokine that circulates in the body and regulates a diverse range of physiologic mechanisms including energy metabolism and insulin sensitivity. In pregnant women, circulating adiponectin levels decrease correspondingly with insulin sensitivity, and adiponectin levels are low in GDM. In this review, we summarize the current state of knowledge about metabolic adaptations to pregnancy and the role of adiponectin in these processes, with a focus on GDM. Recent studies from rodent model systems have clarified that adiponectin deficiency during pregnancy contributes to GDM development. The upregulation of adiponectin alleviates hyperglycemia in pregnant mice, although much remains to be understood for adiponectin to be utilized clinically for GDM.
... Hematoxylin and eosin staining showed fewer hematopoietic cells in the liver of fetuses from HFD-fed dams (Fig. 5D). Consistently, livers of fetuses from HFD-fed dams exhibited a significantly lower density (p < 0.01, Fig. 5D, Table 2), suggesting that maternal HFD consumption might induce fetal fatty liver, as reported in previous studies 45,46 . ...
Maternal overnutrition affects offspring susceptibility to nonalcoholic steatohepatitis (NASH). Male offspring from high-fat diet (HFD)-fed dams developed a severe form of NASH, leading to highly vascular tumor formation. The cancer/testis antigen HORMA domain containing protein 1 (HORMAD1), one of 146 upregulated differentially expressed genes in fetal livers from HFD-fed dams, was overexpressed with hypoxia-inducible factor 1 alpha (HIF-1alpha) in hepatoblasts and in NASH-based hepatocellular carcinoma (HCC) in offspring from HFD-fed dams at 15 weeks old. Hypoxia substantially increased Hormad1 expression in primary mouse hepatocytes. Despite the presence of three putative hypoxia response elements within the mouse Hormad1 gene, the Hif-1alpha siRNA only slightly decreased hypoxia-induced Hormad1 mRNA expression. In contrast, N-acetylcysteine, but not rotenone, inhibited hypoxia-induced Hormad1 expression, indicating its dependency on nonmitochondrial reactive oxygen species production. Synchrotron-based phase-contrast micro-CT of the fetuses from HFD-fed dams showed significant enlargement of the liver accompanied by a consistent size of the umbilical vein, which may cause hypoxia in the fetal liver. Based on these findings, a maternal HFD induces fetal origins of NASH/HCC via hypoxia, and HORMAD1 is a potential therapeutic target for NASH/HCC.
... Some important candidate DELs, such as TCON_00165259 and TCON_00138738, have high expression levels in our data and can target PCK1, could be considered as key candidate genes affecting IMF deposition in pigs. Besides, SCD and ADIPOQ are also pivotal genes that have been reported to affect adipogenesis [33,48]. The results suggest that these lncRNAs might influence IMF deposition by regulating their target genes. ...
Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are important classes of small noncoding RNAs that can regulate numerous biological processes. To understand the role of message RNA (mRNAs, lncRNAs and circRNAs) in the regulation of intramuscular fat (IMF) deposition, in this study the expression profiles of longissimus dorsi (LD) muscle from six Laiwu pigs (three with extremely high and three with extremely low IMF content) were sequenced based on rRNA-depleted library construction. In total, 323 differentially expressed protein-coding genes (DEGs), 180 lncRNAs (DELs) and 105 circRNAs (DECs) were detected between the high IMF and low IMF groups. Functional analysis indicated that most DEGs, and some target genes of DELs, were enriched into GO terms and pathways related to adipogenesis, suggesting their important roles in regulating IMF deposition. In addition, 12 DELs were observed to exhibit a positive relationship with stearoyl-CoA desaturase (SCD), phosphoenolpyruvate carboxykinase 1(PCK1), and adiponectin (ADIPOQ), suggesting they are highly likely to be the target genes of DELs. Finally, we constructed a source gene-circRNA-miRNA connective network, and some of miRNA of the network have been reported to affect lipid metabolism or adipogenesis. Overall, this work provides a valuable resource for further research and helps to understand the potential functions of lncRNAs and circRNAs in IMF deposition.
... Moreover, a complete lack of adiponectin likely leads to compensatory effects as demonstrated in a recent study [32]. In general, the phenotype in APN het mice is not enhanced in APN ko mice [30]. ...
... This difference between our and previous studies could be due to the APN ko mice that were generated by different labs, although they are all on a C56Bl/6 background. We and Qiao et al. [13,30,31] used APN ko mice generated by Scherer's lab [33], while another study used mice generated by Scalia's lab [36]. Moreover, the HF/HS diet did not alter adiponectin levels, which could be explained by the decreased gestational weight gain in the HF/HS fed dams, resulting in similar body weights at gestational day 18.5. ...
... Adiponectin produced by the dam does not pass the placental barrier, as adiponectin is too large (30-kDa protein) to theoretically pass the placenta. This is supported by detecting circulating adiponectin in adiponectin heterozygote dams but not in knockout fetuses, as shown in this study and by others [30]. Adiponectin produced by the fetus cannot pass the placenta either, since no adiponectin was detected in serum from APN ko dams carrying APN het fetuses. ...
Adiponectin administration to pregnant mice decreases nutrient transport and fetal growth. An adiponectin deficiency, on the other hand, as seen in obese women during pregnancy, alters fetal growth; however, the mechanism is unclear. To determine the role of adiponectin on placenta function and fetal growth, we used adiponectin knockout, adiponectin heterozygote that displays reduced adiponectin levels, and wild-type mice on a control diet or high fat/high sucrose (HF/HS) diet. Triglycerides (TGs) in the serum, liver, and placenta were measured using colorimetric assays. Gene expression was measured using quantitative RT-PCR. Adiponectin levels did not affect fetal weight, but it reduced adiponectin levels, increased fetal serum and placenta TG content. Wildtype dams on a HF/HS diet protected the fetuses from fatty acid overload as judged by increased liver TGs in dams and normal serum and liver TG levels in fetuses, while low adiponectin was associated with increased fetal liver TGs. Low maternal adiponectin increased the expression of genes involved in fatty acid transport; Lpl and Cd36 in the placenta. Adiponectin deficiency does not affect fetal growth but induces placental dysfunction and increases fetal TG load, which is enhanced with obesity. This could lead to imprinting effects on the fetus and the development of metabolic dysfunction in the offspring.
... A high concentration of adiponectin in the fetus may enhance the growth-promoting effect of insulin through its insulin-sensitizing action [9]. Studies in mice have shown that fetal adiponectin enhances fetal fat deposition and plays a role in maternal obesity-induced increased birth weight [32]. ...
Background
Cord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines with neonatal adiposity and abdominal fat distribution measured by magnetic resonance imaging (MRI) in an Asian mother–offspring cohort.
Methods
Growing Up in Singapore Towards healthy Outcomes (GUSTO), is a prospective mother–offspring birth cohort study in Singapore. Cord blood plasma leptin and adiponectin concentrations were measured using Luminex and Enzyme-Linked Immunosorbent Assay respectively in 816 infants. A total of 271 neonates underwent MRI within the first 2-weeks after delivery. Abdominal superficial (sSAT), deep subcutaneous (dSAT), and intra-abdominal (IAT) adipose tissue compartment volumes were quantified from MRI images. Multivariable regression analyses were performed.
Results
Indian or Malay ethnicity, female sex, and gestational age were positively associated with cord blood leptin and adiponectin concentrations. Maternal gestational diabetes (GDM) positively associated with cord blood leptin concentrations but inversely associated with cord blood adiponectin concentrations. Maternal pre-pregnancy body mass index (BMI) showed a positive relationship with cord blood leptin but not with adiponectin concentrations. Each SD increase in cord blood leptin was associated with higher neonatal sSAT, dSAT and IAT; differences in SD (95% CI): 0.258 (0.142, 0.374), 0.386 (0.254, 0.517) and 0.250 (0.118, 0.383), respectively. Similarly, each SD increase in cord blood adiponectin was associated with higher neonatal sSAT and dSAT; differences in SD (95% CI): 0.185 (0.096, 0.274) and 0.173 (0.067, 0.278), respectively. The association between cord blood adiponectin and neonatal adiposity was observed in neonates of obese mothers only.
Conclusions
Cord blood leptin and adiponectin concentrations were associated with ethnicity, maternal BMI and GDM, sex and gestational age. Both adipokines showed positive association with neonatal abdominal adiposity.
... In fact, little is known about how increased maternal adipose tissue in pregnancy affects metabolic homeostasis in the developing fetus [9]. Although the altered maternal secretion of adipokines and their concentrations have been previously linked to newborn fat mass percentage [10,11], the molecular mechanisms underlying transmission of obesity risk from mother to offspring are not fully elucidated [12,13]. ...
Genes involved in the regulation of metabolism, adipose tissue deposition, inflammation, and the appetite-satiety axis may play an important role in fetal development, and possibly induce permanent metabolic changes and fat accumulation. In this study we investigated: (1) obesity-related gene expression in maternal and cord blood of overweight/obese and normal-weight pregnant women; (2) associations between obesity-related gene expression in maternal and cord blood; and (3) associations of gene expression in each of maternal and cord blood with newborn adiposity.
Twenty-five overweight/obese and 32 normal-weight pregnant women were selected from the Araraquara Cohort Study according to their pre-pregnancy BMI. Maternal and cord blood gene expression of LEPR, STAT3, PPARG, TLR4, IL-6, IL-10, FTO, MC4R, TNF-α, and NFκB were investigated by relative real-time PCR quantification. The body composition of the newborns was assessed by air displacement plethysmography. Associations between maternal and cord blood gene expression and markers of newborn adiposity (weight, BMI, and fat mass%) were explored by linear regression models controlling for maternal age, pre-pregnancy BMI, maternal gestational weight gain, gestational age, and newborn sex.
There was higher TLR4, NFκB, and TNF-a expression, and lower IL-6 expression, in overweight/obese pregnant women and their respective newborns compared with normal-weight women and their newborns (p < 0.001). Maternal PPARG gene expression was associated with both weight and fat mass % of the newborns, and cord blood IL-10 expression was associated with BMI and fat mass %, controlling for confounders.
To our knowledge, this is the first study to evaluate the relationship of maternal and cord blood gene expression with adiposity markers of the newborn. Our results provide evidence for the contribution of maternal and cord blood gene expression—particularly maternal PPARG and TLR4 expression, and cord blood IL-10 expression—to newborn weight, BMI, and fat mass %.
