Metabolic adjustments to moderate maternal nutrient restriction

Schlabritz‐Loutsevitch, Natalia; Dudley, Christopher; Gomez, Jeremiah J.; Heath, Nevill C.; Smith, Bonnie K.; Jenkins, Susan L.; McDonald, Thomas J.; Bartlett, Thad Q.; Nathanielsz, Peter W.; Nijland, Mark J.

doi:10.1017/s0007114507700727

Cited by 27 publications

(30 citation statements)

References 39 publications

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“…It has been demonstrated in numerous models, including rodents, sheep, and NHPs, that manipulation of the maternal diet or hormone environment can affect the development of metabolic systems in the offspring (15-18, 22-24, 64). Using NHP models, Nathanielsz and colleagues have demonstrated a broad range of metabolic and developmental defects in the offspring of mothers with nutritional restriction (65)(66)(67)(68)(69)(70). These broad effects are surprising, because the animals are nutritionally restricted by only 30%.…”

Section: Discussionmentioning

confidence: 99%

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

McCurdy¹,

Bishop²,

Williams³

et al. 2009

J. Clin. Invest.

422

562

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Maternal obesity is thought to increase the offspring's risk of juvenile obesity and metabolic diseases; however, the mechanism(s) whereby excess maternal nutrition affects fetal development remain poorly understood. Here, we investigated in nonhuman primates the effect of chronic high-fat diet (HFD) on the development of fetal metabolic systems. We found that fetal offspring from both lean and obese mothers chronically consuming a HFD had a 3-fold increase in liver triglycerides (TGs). In addition, fetal offspring from HFD-fed mothers (O-HFD) showed increased evidence of hepatic oxidative stress early in the third trimester, consistent with the development of nonalcoholic fatty liver disease (NAFLD). O-HFD animals also exhibited elevated hepatic expression of gluconeogenic enzymes and transcription factors. Furthermore, fetal glycerol levels were 2-fold higher in O-HFD animals than in control fetal offspring and correlated with maternal levels. The increased fetal hepatic TG levels persisted at P180, concurrent with a 2-fold increase in percent body fat. Importantly, reversing the maternal HFD to a low-fat diet during a subsequent pregnancy improved fetal hepatic TG levels and partially normalized gluconeogenic enzyme expression, without changing maternal body weight. These results suggest that a developing fetus is highly vulnerable to excess lipids, independent of maternal diabetes and/or obesity, and that exposure to this may increase the risk of pediatric NAFLD.

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Section: Discussionmentioning

confidence: 99%

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

McCurdy¹,

Bishop²,

Williams³

et al. 2009

J. Clin. Invest.

422

562

View full text Add to dashboard Cite

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“…Thirty-eight female baboons ( Papio hamadryas anubis ) from the Southwest National Primate Research Center at San Antonio, Texas, USA were recruited for this study and maintained in group housing. The caging system allows control and monitoring of food intake while still permitting normal social and physical activity and has been described in detail [14, 29, 30]. Briefly, groups of 16 females carefully selected to produce a homogeneous group were assembled and socialized in the presence of a vasectomized male while eating Purina Monkey Diet 5038 (Purina, St. Louis, Missouri, USA) ad libitum.…”

Section: Methodsmentioning

confidence: 99%

Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction

Muralimanoharan

Nakayasu

et al. 2017

Journal of Molecular and Cellular Cardiology

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Poor maternal nutrition causes intrauterine growth restriction (IUGR); however, its effects on fetal cardiac development are unclear. We have developed a baboon model of moderate maternal undernutrition, leading to IUGR. We hypothesized that IUGR affects fetal cardiac structure and metabolism. Six control pregnant baboons ate ad-libitum (CTRL)) or 70% CTRL from 0.16 of gestation (G). Fetuses were euthanized at C-section at 0.9G under general anesthesia. Male but not female IUGR fetuses showed left ventricular fibrosis inversely correlated with birth weight. Expression of extracellular matrix protein TSP-1 was increased (p<0.05) in male IUGR s. Expression of cardiac fibrotic markers TGFβ, SMAD3 and ALK-1 were downregulated in male IUGRs with no difference in females. Autophagy was present in male IUGR evidenced by upregulation of ATG7 expression and lipidation LC3B. Global miRNA expression profiling revealed 56 annotated and novel cardiac miRNAs exclusively dysregulated in female IUGR, and 38 cardiac miRNAs were exclusively dysregulated in males (p<0.05). Fifteen (CTRL) and 23 (IUGR) miRNAs, were differentially expressed between males and. females (p<0.05) suggesting sexual dimorphism, which can be at least partially explained by differential expression of upstream transcription factors (e.g. HNF4α, and NFκB p50). Lipidomics analysis of fetal cardiac tissue exhibited a net increase in diacylglycerol and plasmalogens and a decrease in triglycerides and phosphatidylcholines. In summary, IUGR resulting from decreased maternal nutrition is associated with sex-dependent dysregulations in cardiac structure, miRNA expression, and lipid metabolism. If these changes persist postnatally, they may program offspring for higher later life cardiac risk.

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“…at the Southwest National Primate Research Center (SNPRC) in San Antonio, Texas (Schlabritz-Loutsevitch et al 2007). Baboon species are widespread in equatorial Africa.…”

Section: Related Studiesmentioning

confidence: 99%

Calorie Restriction and Aging in Nonhuman Primates

Kemnitz¹

2011

ILAR Journal

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In the 75 years since the seminal observation of Clive McCay that restriction of calorie intake extends the lifespan of rats, a great deal has been learned about the effects of calorie restriction (CR; reduced intake of a nutritious diet) on aging in various short-lived animal models. Studies have demonstrated many beneficial effects of CR on health, the rate of aging, and longevity. Two prospective investigations of the effects of CR on long-lived nonhuman primate (NHP) species began nearly 25 years ago and are still under way. This review presents the design, methods, and main findings of these and other important contributing studies, which have generally revealed beneficial effects of CR on physiological function and the retardation of disease consistent with studies in other species. Specifically, prolonged CR appears to extend the lifespan of rhesus monkeys, which exhibited lower body fat; slower rate of muscle loss with age; lower incidence of neoplasia, cardiovascular disease, type 2 diabetes mellitus, and endometriosis; improved insulin sensitivity and glucose tolerance; and no apparent adverse effect on bone health, as well as a reduction in total energy expenditure. In addition, there are no reports of deleterious effects of CR on reproductive endpoints, and brain morphology is preserved by CR. Adrenal and thyroid hormone profiles are inconsistently affected. More research is needed to delineate the mechanisms of the desirable outcomes of CR and to develop interventions that can produce similar beneficial outcomes for humans. This research offers tremendous potential for producing novel insights into aging and risk of disease.

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Metabolic adjustments to moderate maternal nutrient restriction

Cited by 27 publications

References 39 publications

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates

Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction

Calorie Restriction and Aging in Nonhuman Primates

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