Predictive Adaptive Responses to Maternal High-Fat Diet Prevent Endothelial Dysfunction but Not Hypertension in Adult Rat Offspring

Khan, Imran Y; Dekou, Vasia; Hanson, Mark A.; Poston, Lucilla; Taylor, Paul D.

doi:10.1161/01.cir.0000139843.05436.a0

Cited by 201 publications

(184 citation statements)

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“…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%

“…Considering that a typical Western diet is rich in dietary fat content (17), especially saturated fatty acids (SFA), some studies have investigated the role of high-fat feeding in the concept of developmental origins of health and disease (3)(4)(5). These studies indicate that maternal high-SFA consumption during pregnancy can induce features of metabolic syndrome including dyslipidemia (26,27,35), insulin resistance (57), and hypertension (36,35) in the adult offspring. However, the underlying mechanisms of these effects are not known.…”

mentioning

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: Discussionmentioning

confidence: 68%

mentioning

confidence: 99%

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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“…Relatively little is known about the persistent consequences of maternal obesity for the developing offspring. Some studies in rodents have assessed influences of maternal high-energy diets using only a short time window, generally less than 14 days prior to mating or only during gestation and/or lactation, and have generally failed to achieve obesity in the dam [16,19,20,[24][25][26]. A few, using a prolonged feeding period to induce obesity [17,27,28], have generally switched from a high-energy diet to a control diet postdelivery [28], potentially inducing changes of the milk composition [29].…”

Section: Discussionmentioning

confidence: 99%

Established diet-induced obesity in female rats leads to offspring hyperphagia, adiposity and insulin resistance

et al. 2009

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Aims/hypothesis Accumulating evidence suggests that maternal obesity may increase the risk of metabolic disease in the offspring. We investigated the effects of established maternal diet-induced obesity on male and female offspring appetite, glucose homeostasis and body composition in rats. Methods Female Wistar rats were fed either a standard chow (3% fat, 7% sugar [wt/wt]) or a palatable obesogenic diet (11% fat, 43% sugar [wt/wt]) for 8 weeks before mating and throughout pregnancy and lactation. Male and female offspring of control and obese dams were weaned on to standard chow and assessed until 12 months of age. Results At mating, obese dams were heavier than control with associated hyperglycaemia and hyperinsulinaemia. Male and female offspring of obese dams were hyperphagic (p<0.0001) and heavier than control (p<0.0001) until 12 months of age. NEFA were raised at 2 months but not at 12 months. At 3 months, OGTT showed more pronounced alteration of glucose homeostasis in male than in female offspring of obese animals. Euglycaemic-hyperinsulinaemic clamps performed at 8 to 9 months in female and 10 to 11 months in male offspring revealed insulin resistance in male offspring of obese dams (p<0.05 compared with control). Body compositional analysis at 12 months also showed increased fat pad weights in male and female offspring of obese animals. Conclusions/interpretation Diet-induced obesity in female rats leads to a state of insulin resistance in male offspring, associated with development of obesity and increased adiposity. An increase in food intake may play a role.

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“…Maternal eNOS Genotype Affects Offspring BPrestriction during pregnancy 26 ; an 8-, 6-, and 4-mm Hg increase in nocturnal systolic, mean, and pulse pressures, respectively, in a model of bilateral uterine artery ligation 27 ; and Յ10-and 14-mm Hg increases in diastolic and systolic pressures in offspring of mothers fed a high-fat diet during pregnancy 28,29 ). The available data suggest that, when telemetry methods are used to minimize potential stress-induced artifacts, IUGR is associated with a statistically significant though modest impact on offspring blood pressure.…”

Section: Van Vliet and Chafementioning

confidence: 99%

“…An effect of developmental programming on spontaneous locomotor activity was also described in the rat model of IUGR induced by low maternal protein intake by Tonkiss et al 26 Although reductions in the spontaneous locomotor activity have also been reported in a rat model of developmental programming (induced by a maternal high-fat diet), this was not a consistent observation, being present in only 1 of 6 groups investigated. 28,29 Other reports of reduced activity associated with IUGR 30 -32 have been based on the use of a specialized apparatus in which subjects are placed for short periods of testing. Such tests are likely to evaluate a different aspect of behavior than that provided by longterm telemetric monitoring of spontaneous activity from undisturbed animals in their usual cage and room.…”

Section: Van Vliet and Chafementioning

confidence: 99%

Maternal Endothelial Nitric Oxide Synthase Genotype Influences Offspring Blood Pressure and Activity in Mice

Vliet

Chafe

2007

Hypertension

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Abstract-Deficiencies in maternal endothelial NO synthase (eNOS) have been associated with pregnancy complications, intrauterine growth retardation, and altered vascular function in offspring. In the present study, we investigated the influence of the maternal eNOS genotype on offspring's blood pressure, heart rate, and locomotor activity. The effect of maternal eNOS genotype was made by comparing telemetered blood pressure and activity between 2 groups of 13-to 16-week-old male heterozygous eNOS knockout mice, 1 produced by a cross of eNOS knockout (eNOS Ϫ/Ϫ ) mothers and wild-type (eNOS ϩ/ϩ ) fathers (eNOS ϩ/ϪMAT offspring, Nϭ11), the other by a cross of eNOS ϩ/ϩ mothers and eNOS Ϫ/Ϫ fathers (eNOS ϩ/ϪPAT offspring, Nϭ10). Data were also collected for homozygous eNOS Ϫ/Ϫ and eNOS ϩ/ϩ mice (Nϭ15 each). Heterozygous eNOS knockout mice exhibited blood pressures that were intermediate to the eNOS ϩ/ϩ and eNOS Ϫ/Ϫ groups. Relative to eNOS ϩ/ϪPAT mice, eNOS ϩ/ϪMAT mice exhibited significant increases in nocturnal diastolic arterial pressure and diurnal variations (dark-light difference) in systolic, mean, and diastolic arterial pressure. In addition, indices of spontaneous nocturnal locomotor activity, including both the proportion of time spent active and the intensity of activity when active, were also significantly increased. Heart rate did not differ between the groups. Our results suggest that the maternal eNOS genotype influences both blood pressure and behavior of offspring, possibly as a consequence of developmental programming associated with intrauterine growth retardation. Key Words: experimental hypertension Ⅲ pregnancy Ⅲ developmental programming Ⅲ maternal environment Ⅲ hyperactivity Ⅲ knockout mice Ⅲ telemetry Ⅲ nitric oxide T he characteristics of many physiological systems are influenced by the conditions prevailing during development. 1 Perturbations of the maternal environment that lead to intrauterine growth retardation (IUGR) can have a marked impact on the grown offspring, including increased cardiovascular risk factors (eg, blood pressure and insulin resistance 1,2 ) and reduced adult life span. 3 A wide range of experimental interventions have been used to provoke developmental programming, including disturbances in maternal nutrition (eg, undernutrition and nutritional imbalances 4 ), restriction of uterine blood flow, 5 and the administration of drugs (eg, glucocorticoids 2 and NO synthase inhibitors 6,7 ).A relatively unexplored possibility is that developmental programming could also occur as a consequence of maternal genotype. Maternal endothelial NO synthase (eNOS) is a potential candidate in this regard, because eNOS has been shown to play an important role in the regulation of uterine blood flow, 8,9 and IUGR has been observed in rats treated with inhibitors of NO synthase 6,7 and in mice with targeted deletion of the eNOS gene (eNOS Ϫ/Ϫ ) 8,10 . In humans, polymorphisms of the eNOS gene are common and are associated with endothelial dysfunction, 11-13 increased uterine artery resistan...

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Predictive Adaptive Responses to Maternal High-Fat Diet Prevent Endothelial Dysfunction but Not Hypertension in Adult Rat Offspring

Cited by 201 publications

References 28 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

Established diet-induced obesity in female rats leads to offspring hyperphagia, adiposity and insulin resistance

Maternal Endothelial Nitric Oxide Synthase Genotype Influences Offspring Blood Pressure and Activity in Mice

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