Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth

Rosario, Fredrick J.; Kanai, Yoshikatsu; Powell, Theresa L.; Jansson, Thomas

doi:10.1002/oby.21165

Cited by 104 publications

(130 citation statements)

References 38 publications

(50 reference statements)

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“…We recently established a mouse model of maternal dietinduced obesity, which is associated with maternal glucose intolerance and decreased circulating levels of HMW ADN and fetal overgrowth (19). The placentas of obese dams exhibit activation of insulin and mTORC1 signaling and greater nutrient transport capacity, in agreement with obese women giving birth to large babies (6).…”

Section: Discussionmentioning

confidence: 98%

“…Maternal-facing layer II TPM of the mouse placenta, which is functionally analogous to the human microvillus membrane, was isolated using differential ultracentrifugation and Mg 2+ precipitation, as previously described (19,22). TPM enrichment, as determined by alkaline phosphatase activity of TPM/homogenate, was similar across the different groups (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…We recently established a mouse model of obesity in pregnancy, which shows extensive similarities to the human condition, including low maternal ADN and glucose intolerance, increased placental nutrient transport, and fetal overgrowth (19). In this study, we used this model to test the hypothesis that ADN Significance Obesity and metabolic syndrome may, in part, originate in fetal life.…”

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confidence: 99%

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Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

Aye

Rosario

Powell

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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132

136

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Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/ 6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.adipokines | maternal-fetal exchange | amino acids | glucose | insulin resistance

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

Aye

Rosario

Powell

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

132

136

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“…Several studies using rodent models have been performed to identify the consequences of maternal obesity for foetal development [25,27]. This study fed pregnant mice with HFD to mimic human overnutrition during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, animal models was provided an attractive alternative for possible mechanisms of and therapeutics to GDM [5,6]. Many groups have fed mice an HFD before or during pregnancy and evaluated insulin resistance, obesity, and foetal overgrowth, which are all well-established phenotypes in GDM [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Global mRNA and Long Non-Coding RNA Expression in the Placenta and White Adipose Tissue of Mice Fed a High-Fat Diet During Pregnancy

Huang

Niu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gestational diabetes mellitus (GDM) is a common complication of pregnancy, but the mechanisms underlying the disorders remain unclear. The study aimed to identify mRNA and long non-coding RNA (lncRNA) profiles in placenta and gonadal fat of pregnant mice fed a high-fat diet and to investigate the transcripts and pathways involved in the development of gestational diabetes mellitus. Methods: Deep and broad transcriptome profiling was performed to assess the expression of mRNAs and lncRNAs in placenta and gonadal fat from 3 mice fed an HFD and chow during pregnancy. Then, differentially expressed mRNAs and lncRNAs were validated by quantitative real-time PCR. The function of the differentially expressed mRNAs was determined by pathway and Gene Ontology (GO) analyses, and the physical or functional relationships between the lncRNAs and the corresponding mRNAs were determined. Results: Our study revealed that 82 mRNAs and 52 lncRNAs were differentially expressed in the placenta of mice fed an HFD during pregnancy, and 202 mRNAs and 120 lncRNAs were differentially expressed in gonadal fat. GO and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed differentially expressed mRNAs of placenta were closely related to extracellular matrix interactions, digestion, adhesion, and metabolism, whereas the differentially expressed mRNAs in adipose tissue were related to metabolic and insulin signalling pathways. The gene network demonstrated that Actg2, Cnfn, Muc16, Serpina3k, NONMMUT068202, and NONMMUT068203, were the core of the network in placental tissue, and the genes Tkt, Acss2, and Elovl6 served as the core of the network in gonadal fat tissue. Conclusion: These newly identified key genes and pathways in mice might provide valuable information regarding the pathogenesis of GDM and might be used to improve early diagnosis, prevention, drug design, and clinical treatment.

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Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring

et al. 2019

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Obesity during pregnancy has been shown to increase the risk of metabolic diseases in the offspring. However, the factors within the maternal milieu which affect offspring phenotypes and the underlying mechanisms remain unknown. The adipocyte hormone leptin plays a key role in regulating energy homeostasis and is known to participate in sex‐specific developmental programming. To examine the action of leptin on fetal growth, placental gene expression and postnatal offspring metabolism, we injected C57BL mice with leptin or saline on gestational day 12 and then measured body weights (BWs) of offspring fed on a standard or obesogenic diet, as well as mRNA expression levels of insulin‐like growth factors and glucose and amino acid transporters. Male and female offspring born to leptin‐treated mothers exhibited growth retardation before and a growth surge after weaning. Mature male offspring, but not female offspring, exhibited increased BWs on a standard diet. Leptin administration prevented the development of hyperglycaemia in the obese offspring of both sexes. The placentas of the male and female foetuses differed in size and gene expression, and leptin injection decreased the fetal weights of both sexes, the placental weights of the male foetuses and placental gene expression of the GLUT1 glucose transporter in female foetuses. The data suggest that mid‐pregnancy is an ontogenetic window for the sex‐specific programming effects of leptin, and these effects may be exerted via fetal sex‐specific placental responses to leptin administration.

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Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth

Cited by 104 publications

References 38 publications

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

Global mRNA and Long Non-Coding RNA Expression in the Placenta and White Adipose Tissue of Mice Fed a High-Fat Diet During Pregnancy

Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring

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