Maternal Protein Restriction in the Rat Inhibits Placental Insulin, mTOR, and STAT3 Signaling and Down-Regulates Placental Amino Acid Transporters

Rosario, Fredrick J.; Jansson, Nina; Kanai, Yoshikatsu; Prasad, Puttur D.; Powell, Theresa L.; Jansson, Thomas

doi:10.1210/en.2010-1153

Cited by 152 publications

(151 citation statements)

References 72 publications

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“…Evidence from experimental animals shows that placental structure, growth, and function are directly affected by maternal nutrient availability and/or perturbations to the maternal environment [29,[58][59][60][61][62][63]. These changes will directly influence placental transfer of solutes and oxygen to the fetus and will alter hormone secretion and the release of signaling molecules into the fetal circulation [2].…”

Section: Placental Responses To Changes In Maternal Supplymentioning

confidence: 99%

“…The placental response to changes in maternal oxygen and nutrient supply includes alterations in the expression and/or function of nutrient transporters [31,58,62,75,76]. For instance, maternal undernutrition or restricted utero-placental blood flow results in down-regulation of placental nutrient transporters and, consequently, decreased fetal nutrient availability.…”

Section: Placental Responses To Changes In Maternal Supplymentioning

confidence: 99%

“…Placental AMPK phosphorylation has been reported to be increased in sheep subjected to 50% calorie restriction [100] and decreased in overnourished, obese pregnant ewes [101], high-fat diet-fed pregnant rats [97], and obese women giving birth to large babies [89]. In contrast, placental AMPK activity is unaltered in response to maternal protein restriction in the rat [62]. Although AMPK phosphorylation constitutes a proxy for tissue ATP levels, more detailed studies are needed to better understand placental energy sensing and the link between placental energy metabolism and fetal growth.…”

Section: Placental Signaling Pathways Responding To Altered Metabolismentioning

confidence: 99%

“…Placental mTORC1 activity is inhibited in human IUGR [96,114] and activated in placentas of large babies born to obese mothers [97]. Furthermore, placental mTORC1 activity has been reported to be decreased in hyperthermia-induced IUGR in the sheep [117] and in response to a maternal low-protein diet in the rat [62] and maternal calorie restriction in the baboon [27].…”

Section: The Role Of Mtor In Placental Nutrient Sensingmentioning

confidence: 99%

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The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

Díaz

Powell

Jansson

2014

Biology of Reproduction

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124

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The placenta mediates maternal-fetal exchange and has historically been regarded as a passive conduit for nutrients. However, emerging evidence suggests that the placenta actively responds to nutritional and metabolic signals from the mother and the fetus. We propose that the placenta integrates a multitude of maternal and fetal nutritional cues with information from intrinsic nutrient-sensing signaling pathways to match fetal demand with maternal supply by regulating maternal physiolo-

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Section: Placental Responses To Changes In Maternal Supplymentioning

confidence: 99%

Section: Placental Responses To Changes In Maternal Supplymentioning

confidence: 99%

Section: Placental Signaling Pathways Responding To Altered Metabolismentioning

confidence: 99%

Section: The Role Of Mtor In Placental Nutrient Sensingmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

Díaz

Powell

Jansson

2014

Biology of Reproduction

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124

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“…System L consists of a light chain (L-type amino acid transporter [LAT] 1 or LAT2) and a heavy chain (4F2hc/CD98). The activity of placental amino acid transporters System L and System A has been associated with maternal nutritional status [7,8], with maternal overnutrition and undernutrition being linked to increased and decreased placental amino acid transport, respectively [30,31]. Moreover, placental System L and System A activities are decreased in IUGR pregnancies [32][33][34][35] and increased with fetal overgrowth [20,30,36] in humans and relevant animal models.…”

Section: Introductionmentioning

confidence: 99%

Maternal Overweight Induced by a Diet with High Content of Saturated Fat Activates Placental mTOR and eIF2alpha Signaling and Increases Fetal Growth in Rats1

Gaccioli

White

Capobianco

et al. 2013

Biology of Reproduction

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The mammalian target of rapamycin (mTOR) and the eukaryotic initiation factor 2 (eIF2) signaling pathways control protein synthesis in response to nutrient availability. Moreover, mTOR is a positive regulator of placental nutrient transport and is involved in the regulation of fetal growth. We hypothesized that maternal overweight, induced by a diet with high saturated fat content, i) up-regulates placental mTOR activity and nutrient transport, resulting in fetal overgrowth; ii) inhibits phosphorylation of eIF2 at its alpha subunit (eIF2alpha); and iii) leads to placental inflammation. Albino Wistar female rats were fed a control or high-saturated-fat (HF) diet for 7 wk before mating and during pregnancy. At gestational day 21, the HF diet significantly increased maternal and fetal triglyceride, leptin, and insulin (but not glucose) levels and maternal and fetal weights, and placental weights trended to increase. Phosphorylated 4EBP1 (T37/46 and S65) was significantly higher, and phosphorylated rpS6 (S235/236) tended to increase, in the placentas of dams fed an HF diet, indicating an activation of mTOR complex 1 (mTORC1). Phosphorylation of AMPK and eIF2alpha was reduced in the HF diet group compared to the control. The expression and activity of placental nutrient transporters and lipoprotein lipase (LPL), as well as the activation of inflammatory pathways, were not altered by the maternal diet. We conclude that maternal overweight induced by an HF diet stimulates mTORC1 activity and decreases eIF2alpha phosphorylation in rat placentas. We speculate that these changes may up-regulate protein synthesis and contribute to placental and fetal overgrowth.

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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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Maternal Protein Restriction in the Rat Inhibits Placental Insulin, mTOR, and STAT3 Signaling and Down-Regulates Placental Amino Acid Transporters

Abstract: Maternal endocrine and metabolic control of placental nutrient transport reduces fetal growth in response to protein restriction.

Cited by 152 publications

References 72 publications

The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

Maternal Overweight Induced by a Diet with High Content of Saturated Fat Activates Placental mTOR and eIF2alpha Signaling and Increases Fetal Growth in Rats1

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

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