High–saturated-fat diet induces gestational diabetes and placental vasculopathy in C57BL/6 mice

Liang, Chengya; Decourcy, Kristi R.; Prater, M. Renée

doi:10.1016/j.metabol.2009.10.015

Cited by 112 publications

(86 citation statements)

References 35 publications

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“…Placentas from preeclamptic pregnancies have increased placental oxidative stress and ET-1 binding (8,22). These data are interesting in light of the findings that mice with HFD-induced obesity and insulin resistance have placental oxidative stress and reductions in trophoblast numbers (96).…”

Section: Effects Of Obesity On the Placental Function And Perfusionmentioning

confidence: 81%

Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms

Spradley

Palei

Granger

2015

American Journal of Physiology-Regulatory, Integrative and Comp

115

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) is a pregnancy-specific disorder typically presenting as new-onset hypertension and proteinuria. While numerous epidemiological studies have demonstrated that obesity increases the risk of PE, the mechanisms have yet to be fully elucidated. Growing evidence from animal and human studies implicate placental ischemia in the etiology of this maternal syndrome. It is thought that placental ischemia is brought about by dysfunctional cytotrophoblast migration and invasion into the uterus and subsequent lack of spiral arteriole widening and placental perfusion. Placental ischemia/ hypoxia stimulates the release of soluble placental factors into the maternal circulation where they cause endothelial dysfunction, particularly in the kidney, to elicit the clinical manifestations of PE. The most recognized of these factors are the anti-angiogenic sFlt-1 and pro-inflammatory TNF-␣ and AT1-AA, which promote endothelial dysfunction by reducing levels of the provasodilator nitric oxide and stimulating production of the potent vasoconstrictor endothelin-1 and reactive oxygen species. We hypothesize that obesity-related metabolic factors increase the risk for developing PE by impacting various stages in the pathogenesis of PE, namely, 1) cytotrophoblast migration and placental ischemia; 2) release of soluble placental factors into the maternal circulation; and 3) maternal endothelial and vascular dysfunction. This review will summarize the current experimental evidence supporting the concept that obesity and metabolic factors like lipids, insulin, glucose, and leptin affect placental function and increase the risk for developing hypertension in pregnancy by reducing placental perfusion; enhancing placental release of soluble factors; and by increasing the sensitivity of the maternal vasculature to placental ischemia-induced soluble factors. body mass index; inflammation; placental ischemia; pregnancy; RUPP; sFlt-1 PE IS A PREGNANCY-SPECIFIC DISORDER typically identified by new-onset hypertension in the second half of pregnancy. Although often accompanied by new-onset proteinuria, PE can be associated with many other signs and symptoms including headaches, visual disturbances, epigastric pain, and the development of edema (4,192). Globally, this disease affects over 8 million pregnancies per year and is estimated to account for 40 -60% of maternal deaths in developing countries (125). In the United States, there was a 25% increase in the rate of PE between the years 1987-2004 (189). This significant increase highlights the importance of understanding how risk factors like obesity play a role in the pathogenesis of this maternal syndrome. Obesity is defined as a body mass index (BMI) of greater than or equal to 30 kg/m 2 . Greater than one-half of pregnant women are overweight or obese (48), and more than two-thirds of reproductive-aged women in the United States are overweight or obese (49). Although mounting epidemiological evidence supports obesity as a major risk factor for PE, the mechanisms linking these two morbidities are...

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Section: Effects Of Obesity On the Placental Function And Perfusionmentioning

confidence: 81%

Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms

Spradley

Palei

Granger

2015

American Journal of Physiology-Regulatory, Integrative and Comp

115

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“…A recent study (Liang et al, 2009a) showed that the gestational diabetes mellitus-induced placental oxidative stress in mice were significantly mitigated by quercetin supplementation. Results from this report also revealed that quercetin partially decreased maternal hyperglycemia and hyperinsulinemia, and offer additional information about preventive and therapeutic management of gestational diabetes mellitus, a commonly encountered disorder of mid to late pregnancy.…”

Section: Insulin Resistancementioning

confidence: 99%

Flavonols and cardiovascular disease

Pérez‐Vizcaíno

Duarte

2010

Molecular Aspects of Medicine

330

197

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“…They found that diabetes was not present prior to mating, but was confirmed at gestation day 20, resembling a GDM model. Liang et al used a similar protocol in mice, but diabetes was developed pre-gestational in this study [60]. In sheep, a 60 days of diabetogenic diet before mating resulted in insulin resistance and increased fetal adipose tissue and β cell mass in mid-gestation (gestation day 75) [61].…”

Section: Diet-induced Diabetic Pregnancymentioning

confidence: 89%

Animal Models of Fetal Medicine and Obstetrics

Andersen¹,

Alstrup²,

Duvald³

et al. 2018

Experimental Animal Models of Human Diseases - An Effective Therapeutic Strategy

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Animal models remain essential to understand the fundamental mechanisms occurring in fetal medicine and obstetric diseases, such as intrauterine growth restriction, preeclampsia and gestational diabetes. These vary regarding the employed method used for induction of the disease, and differ in relation to the animal characteristics (size, number of fetuses, placenta barrier type, etc.). While none of these exactly mirrors the human condition, different pregnant animal models (mice, rats, guinea pigs, chinchillas, rabbits, sheep and pigs) are here described with respect to advantages and limitations. The ability to employ noninvasively diagnostics varies among species, specifically for ultrasound and clinical magnetic resonance imaging procedures. Management of feeding, handling, care and anesthesia are particularly important factors in the pregnant animal.

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High–saturated-fat diet induces gestational diabetes and placental vasculopathy in C57BL/6 mice

Cited by 112 publications

References 35 publications

Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms

Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms

Flavonols and cardiovascular disease

Animal Models of Fetal Medicine and Obstetrics

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