Differential body weight, blood pressure and placental inflammatory responses to normal versus high-fat diet in melanocortin-4 receptor-deficient pregnant rats

Spradley, Frank T.; Palei, Ana C.; Granger, Joey P.

doi:10.1097/hjh.0000000000001059

Cited by 8 publications

(10 citation statements)

References 48 publications

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“…In the current study, we set forth to explore the importance of MC4R in control of blood pressure during normal pregnancy and in response to RUPP. In MC4R-def pregnant rats, we previously showed and confirmed here that they have elevated body weight, fat mass, and blood pressure under normal pregnant conditions 34 . Moreover, our novel finding is that MC4R-def pregnant rats have attenuated placental ischemia-induced hypertension.…”

Section: Discussionsupporting

confidence: 85%

“…Nor did this study delve into the timeframe for the development of hypertension in our obese pregnant model. We previously published that pre-pregnancy body weight is greater in MC4R-def versus that WT rats 34 . In the current study, our focus was on the impact of MC4R deficiency on placental ischemia-induced hypertension towards the end of pregnancy.…”

Section: Discussionmentioning

confidence: 92%

“…We utilized a genetically obese pregnant rat model having heterozygous MC4R deficiency. The purpose for using a genetic model of obesity in rats was based on our previous studies where there were no dramatic changes in body weight or fat mass following high-fat diet feeding in female pregnant rats 33, 34 . Other studies suggest that high-fat diet increases central MC4R signaling 35 , but it has not been examined whether high fat feeding or obesity alters placental ischemia-induced hypertension via MC4R signaling.…”

Section: Discussionmentioning

confidence: 99%

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Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats

et al. 2019

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Preeclampsia (PE) is a pregnancy-specific disorder of new-onset hypertension linked to placental ischemia. While obesity is a major risk factor for PE, not all obese pregnant women develop pregnancy-induced hypertension or PE. Previously, we reported that placental ischemia-induced hypertension is dependent upon intact signaling of the sympathetic nervous system (SNS). Moreover, in various models of obesity, blockade of melanocortin-4 receptor (MC4R) signaling protects against the development of hypertension via suppression of the SNS. Less is known regarding this pathway during obese pregnancy. Although blockade of MC4R may lead to increased body weight during pregnancy, we tested the hypothesis that placental ischemia-induced hypertension is attenuated in obese MC4R-deficient pregnant rats. On gestational day (GD) 14, MC4R wild type (WT) or heterozygous-deficient (MC4R-def) rats were subjected to chronic placental ischemia via the reduced uterine perfusion pressure (RUPP) procedure or Sham surgery then examined on GD19. In Sham MC4R-def vs. Sham WT pregnant rats, there was increased body weight, fat mass, and circulating leptin levels but they had similar fetus weights. RUPP reduced fetus weights in both strains. RUPP increased blood pressure in WT rats but this response was significantly attenuated in MC4R-def rats, even though blood pressure was elevated in Sham MC4R-def over Sham WT. These data indicate that while obese MC4R-def pregnant rats have higher blood pressure during pregnancy, placental ischemia-induced hypertension is attenuated in obese MC4R-def pregnant rats. Thus, obese women with abnormal MC4R signaling may be less susceptible to the development of placental ischemia-induced hypertension.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats

et al. 2019

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“…What has been studied are the consequences of HFD on pregnancies in the P generation of dams. We previously showed that HFD feeding from early age and continued through pregnancy resulted in a slight increase in fat weight and elevated blood pressure by the end of pregnancy at gestational day 19 in rats [ 5 ]. Others have also reported that HFD promotes increased fat weight in the P generation during their pregnancies [ 6 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

High-fat diet from parental generation exaggerates body and adipose tissue weights in pregnant offspring

Spradley

2020

PLoS ONE

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Parental high-fat diet (HFD) programs for obesity and hypertension in female offspring in rats, but it is unknown how the pregnancies of these offspring are impacted. Therefore, the hypothesis was tested that parental HFD exaggerates obesity and hypertension during pregnancy of the offspring. Wistar Hannover rat dams (the parental, P generation) were maintained on normal-fat diet (NFD) or HFD from weaning and were kept on respective diets through pregnancy and lactation. Their offspring (the first filial, F1 generation) were weaned onto the same diet as the P generation, or they were changed to the other diet to determine if combined HFD in the P and F1 generations exaggerates body weight and blood pressure levels during pregnancy in these offspring. This diet paradigm resulted in the following groups of pregnant F1 offspring: P-NFD/F1-NFD, P-HFD/F1-NFD, P-NFD/F1-HFD, and P-HFD/F1-HFD. Maternal body and adipose tissue weights were greatest in the P-HFD/F1-HFD group compared to the other 3 groups by the end of pregnancy. Plasma leptin and conscious mean arterial blood pressure were not significantly different between any group, although there was a main effect for increased blood pressure in the F1-HFD groups. Circulating levels of the antihypertensive pregnancy factor, placental growth factor (PlGF), were assessed. Although average PlGF levels were similar among all groups, correlative studies revealed that lower levels of PlGF were associated with higher blood pressure only in the P-HFD/F1-HFD group. In summary, HFD feeding from the P generation exaggerated HFD-induced body and adipose tissue weights in the pregnant offspring.

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“…The SAP elevation before pregnancy in rats with HFD (Fig 1) are associated to increases in fat abdominal volume and leptin, and a decrease in adiponectin [12]. Epidemiological and experimental studies showed that AP is elevated at the middle and at the end of gestation in obese subjects [30] but they did not examine whether AP was already elevated before pregnancy. This study reports novel findings showing that AP does not change significantly throughout gestation in rats with an early and prolonged exposure to a HFD.…”

Section: Discussionmentioning

confidence: 97%

Cardiac, renal and uterine hemodynamics changes throughout pregnancy in rats with a prolonged high fat diet from an early age

et al. 2020

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Objective To examine whether the cardiac, renal and uterine physiological hemodynamic changes during gestation are altered in rats with an early and prolonged exposure to a high fat diet (HFD). Methods Arterial pressure and cardiac, renal, uterine and radial arteries hemodynamic changes during gestation were examined in adult SD rats exposed to normal (13%) (n = 8) or high (60%) (n = 8) fat diets from weaning. Plethysmography, high-resolution high-frequency ultrasonography and clearance of an inulin analog were used to evaluate the arterial pressure and hemodynamic changes before and at days 7, 14 and 19 of gestation. Results Arterial pressure was higher (P<0.05) in rats with high than in those with normal (NFD) fat diet before pregnancy (123 ±3 and 110 ±3 mmHg, respectively) and only decreased at day 14 of gestation in rats with NFD (98±4 mmHg, P<0.05). A significant increment in stroke volume (42 ±10%) and cardiac output (51 ±12%) was found at day 19 of pregnancy in rats with NFD. The changes in stroke volume and cardiac output were similar in rats with NFD and HFD. When compared to the values obtained before pregnancy, a transitory elevation in renal blood flow was found at day 14 of pregnancy in both groups. However, glomerular filtration rate only increased (P<0.05) in rats with NFD at days 14 (20 ±7%) and 19 (27 ±8%) of gestation. The significant elevations of mean velocity, and velocity time integral throughout gestation in radial (127 ±26% and 111 ±23%, respectively) and uterine (91 ±16% and 111 ±25%, respectively) arteries of rats with NFD were not found in rats with an early and prolonged HFD.

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Differential body weight, blood pressure and placental inflammatory responses to normal versus high-fat diet in melanocortin-4 receptor-deficient pregnant rats

Cited by 8 publications

References 48 publications

Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats

Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats

High-fat diet from parental generation exaggerates body and adipose tissue weights in pregnant offspring

Cardiac, renal and uterine hemodynamics changes throughout pregnancy in rats with a prolonged high fat diet from an early age

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