Offspring of Normal and Diabetic Rats Fed Saturated Fat in Pregnancy Demonstrate Vascular Dysfunction

Koukkou, E; Ghosh, Pradip; Lowy, C.; Poston, Lucilla

doi:10.1161/01.cir.98.25.2899

Cited by 91 publications

(81 citation statements)

References 24 publications

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“…Thus, vascular reactivity was expected to change in the presence of high levels of LDL cholesterol, especially in the female offspring. Increased vascular contractility and decreased vasodilator capacity has been observed in adult models of maternal overnutrition and CVD (25,37,38). Feeding a high-SFA maternal diet caused a reduction in vascular contractility, whereas vasodilator capacity was unaffected in our study.…”

Section: Discussionsupporting

confidence: 50%

“…L-NAME caused a small increment in the contractile responses to KCl and PE in S/C males, which would be consistent with our hypothesis. Previous studies dealing with maternal overnutrition during pregnancy have indicated an impairment of AChinduced vasorelaxation, albeit using smaller-caliber resistancetype arteries, where the endothelial-derived relaxing factors differ from those present in aorta, e.g., endothelium-derived hyperpolarizing factor (26,35,36,38). Female offspring did not show any alterations in the relaxation responses to ACh and SNP.…”

Section: Discussionmentioning

confidence: 68%

“…Maternal high-fat intake has also been reported to generate reactive oxygen species (ROS) and oxidative stress, which has been linked to vascular disorders in the offspring (25,38). It has been reported that increased ROS generation can lead to increased production of hydrogen peroxide in vascular cells that can act as an endothelial-derived relaxing factor and can induce the vasodilation of aortic vessels in response to ACh (42), despite the presence of endothelial dysfunction (49).…”

Section: Discussionmentioning

confidence: 99%

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Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor

Chechi

McGuire²,

Cheema³

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Chechi K, McGuire JJ, Cheema SK. Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor. Am J Physiol Regul Integr Comp Physiol 296: R1029 -R1040, 2009. First published February 4, 2009 doi:10.1152/ajpregu.90932.2008We have previously shown that a maternal high-fat diet, rich in saturated fatty acids (SFA), alters the lipid metabolism of their adult offspring. The present study was designed to investigate 1) whether alterations in hepatic LDL-receptor (LDL-r) expression may serve as a potential mechanism of developmental programming behind the altered lipid metabolism of the offspring, 2) whether altered lipid metabolism leads to aortic vascular dysfunction in the offspring, 3) whether deleterious effects of SFA exposure preweaning are influenced by postweaning diet, and 4) whether gender-specific programming effects are observed. Female C57Bl/6 mice were fed a high-SFA diet or regular chow during gestation and lactation while their pups, both male and female, received either SFA or a chow diet after weaning. Male offspring obtained from mothers fed an SFA diet and those who continued on chow postweaning had higher plasma triglycerides and total cholesterol, whereas female offspring had higher plasma total and LDL cholesterol levels, lower hepatic LDL-r mRNA expression, and reduced aortic contractile responses compared with the offspring that were fed chow throughout the study. A comparison of the postweaning diet revealed significantly lower hepatic LDL-r expression along with significantly higher plasma LDL-cholesterol concentration in the female offspring that were obtained from mothers fed an SFA diet and who continued on an SFA diet postweaning, compared with the female offspring that were obtained from mothers fed an SFA diet but who continued on chow postweaning. In conclusion, we report a novel observation of hepatic LDL-r-mediated programming of altered lipid metabolism, along with aortic vascular dysfunction, in the female offspring of mothers fed a high-SFA diet. Male offspring only exhibited dyslipidemia, suggesting gender-mediated programming. This study further highlighted the role of postweaning diets in overriding the effects of maternal programming. fetal programming; plasma lipids; hepatic LDL-receptor; dietary fats; cardiovascular disease RECENT EVIDENCE BASED ON THE developmental origins of health and disease hypothesis suggests that early nutrition can be critical in determining the cardiovascular health of an individual (43, 44). According to this hypothesis, which was originally known as Barker's hypothesis, an adverse maternal nutrition during gestation can create a stressed environment for the developing fetus. The fetus responds to this nutritional stress by programming its own growth in a way that could increase its risk of developing metabolic disorders in later life (6 -8). Considering that a typical Western diet is rich in dietary fat content (17), especially saturated fatty acids (SFA), s...

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor

Chechi

McGuire²,

Cheema³

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…A loss of AA and DHA would reduce liquidity and the liberal mechanical properties normal to active cell membranes. Such a defect in the endothelial membrane could create susceptibility to vascular dysfunction as experimentally demonstrated in rats [46,47].…”

Section: Discussionmentioning

confidence: 99%

Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes

et al. 2004

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Aims/hypothesis. Gestational diabetes is a metabolic disorder affecting 2-5% of women and is a predictor of obesity, Type 2 diabetes mellitus and cardiovascular disease. Insulin resistance, a characteristic of gestational diabetes and obesity, is correlated with the fatty acids profile of the red cell and skeletal muscle membranes. We investigated the plasma and red cell fatty acid status of gestational diabetes. The effect of obesity on membrane fatty acids was also examined. Methods. Fasting blood obtained at diagnosis was analysed for the fatty acids in plasma choline phosphoglycerides and red cell choline and ethanolamine phosphoglycerides.Results. There were reductions in arachidonic acid (controls 10.74±2.35 vs gestational diabetes 8.35±3.49, p<0.01) and docosahexaenoic acid (controls 6.31± 2.67 vs gestational diabetes 3.25±2.00, p<0.0001) in the red cell choline phosphoglycerides in gestational diabetes. A similar pattern was found in the ethanolamine phosphoglycerides. Moreover, the arachidonic and docosahexaenoic acids depletion in the red cell choline phosphoglycerides was much greater in overweight/obese gestational diabetes (arachidonic acid= 7.49±3.37, docosahexaenoic acid=2.98±2.18, p<0.01) compared with lean gestational diabetes (arachidonic acid=10.03±2.74, docosahexaenoic acid=4.18±1.42). Conclusion/interpretation. Apparently normal plasma choline phosphoglycerides fatty acids profile in the gestational diabetic women suggested that membrane lipid abnormality is associated specifically with perturbation in the membrane. The fact that the lipid abnormality is more pronounced in the outer leaflet of the membrane where most of receptor binding and enzyme activities take place might provide an explanation for the increased insulin resistance in gestational diabetes and obesity. [Diabetologia (2004) 47:75-81]

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“…In addition, previous studies have provided evidence that individual fatty acids have distinct roles in development. The n-3 LCPUFA are recognised as essential fatty acids for fetal and infant development, particularly the development of the brain and central nervous system [9], while perinatal exposure to excess levels of saturated or trans fats during has been linked to an increased risk of obesity, insulin resistance and cardiovascular deficits [10,11]. Consequently, it is important to understand the impact of maternal diet on the balance of specific fatty acids in the milk.…”

Section: Introductionmentioning

confidence: 99%

Effect of a maternal cafeteria diet on the fatty acid composition of milk and offspring red blood cells

Vithayathil

Gugusheff

Gibson

et al. 2016

Prostaglandins, Leukotrienes and Essential Fatty Acids

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In all cases accepted manuscripts should:  link to the formal publication via its DOI  bear a CC-BY-NC-ND license -this is easy to do, click here to find out how  if aggregated with other manuscripts, for example in a repository or other site, be shared in alignment with our hosting policy  not be added to or enhanced in any way to appear more like, or to substitute for, the published journal article ABSTRACTPrevious studies have demonstrated that exposure to a maternal cafeteria diet during the lactation period alone produces detrimental effects to offspring metabolic health comparable to exposure during the entire perinatal period. The present study used a rodent model to assess the effect of a maternal cafeteria diet on the fat content and fatty acid composition of the dams' milk, and to determine the degree to which this was related to the fatty acid status of offspring on postnatal day 1 (PND1), weaning and 3 weeks post-weaning onto a standard rodent diet. As expected, omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) content of both the milk and pup red blood cells (RBCs) was lower in the cafeteria (CAF) group on PND1. At 2 weeks post-partum, milk produced by CAF dams had a higher total fat, saturated fat and n-6 PUFA content, however these differences were modest in comparison with the differences in maternal intake between groups. Offspring suckled by CAF dams had a lower n-3 LCPUFA and n-6 PUFA status at weaning and higher trans fatty acid levels at both weaning and 6 weeks of age. These findings indicate that the fat content and fatty acid composition of the dam's milk is altered by exposure to a cafeteria diet. While it appears that the dam has a significant capacity to buffer the transfer of most dietary lipids into the milk, the trans fatty acids in particular appear to be readily transferred, resulting in persistent increases in trans fatty acid status of the offspring after weaning. The potential physiological implications of this warrants further explanation.

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Offspring of Normal and Diabetic Rats Fed Saturated Fat in Pregnancy Demonstrate Vascular Dysfunction

Abstract: A high-fat diet in pregnancy led to vascular dysfunction in rat weanlings and young adult offspring. Vascular function further deteriorated in weanlings if the maternal rat was diabetic.

Cited by 91 publications

References 24 publications

Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor

Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor

Adverse effect of obesity on red cell membrane arachidonic and docosahexaenoic acids in gestational diabetes

Effect of a maternal cafeteria diet on the fatty acid composition of milk and offspring red blood cells

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