Influence of moderate maternal nutrition restriction on the fetal baboon metabolome at 0.5 and 0.9 gestation

Hellmuth, Christian; Uhl, Olaf; Kirchberg, Franca F.; Harder, Ulrike; Peißner, Wolfgang; Koletzko, Berthold; Nathanielsz, Peter W.

doi:10.1016/j.numecd.2016.04.004

Cited by 11 publications

(10 citation statements)

References 37 publications

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“…During midgestation, maternal undernutrition alters the liver weight of fetuses in sheep [7, 14–16] and cattle [17], affects insulin secretion [7], hepatic gene expression and epigenetic modification of gluconeogenic enzyme in sheep [16], and changes the fetal liver metabolite profile in baboons [18]. These studies partly reveal the effects on liver function in fetuses or in adult offspring.…”

Section: Introductionmentioning

confidence: 99%

Evidence for liver energy metabolism programming in offspring subjected to intrauterine undernutrition during midgestation

et al. 2019

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BackgroundMaternal undernutrition programs fetal energy homeostasis and increases the risk of metabolic disorders later in life. This study aimed to identify the signs of hepatic metabolic programming in utero and during the juvenile phase after intrauterine undernutrition during midgestation.MethodsFifty-three pregnant goats were assigned to the control (100% of the maintenance requirement) or restricted (60% of the maintenance requirement from day 45 to day 100 of midgestation and realimentation thereafter) group to compare hepatic energy metabolism in the fetuses (day 100 of gestation) and kids (postnatal day 90).ResultsUndernutrition increased the glucagon concentration and hepatic hexokinase activity, decreased the body weight, liver weight and hepatic expression of G6PC, G6PD, and PGC1α mRNAs, and tended to decrease the hepatic glycogen content and ACOX1 mRNA level in the dams. Maternal undernutrition decreased the growth hormone (GH) and triglyceride concentrations, tended to decrease the body weight and hepatic hexokinase activity, increased the hepatic PCK1, PCK2 and PRKAA2 mRNAs levels and glucose-6-phosphatase activity, and tended to increase the hepatic PRKAB1 and CPT1α mRNAs levels in the male fetuses. In the restricted female fetuses, the hepatic hexokinase activity and G6PC mRNA level tended to be increased, but PKB1 mRNA expression was decreased and the ACACA, CPT1α, NR1H3 and STK11 mRNA levels tended to be decreased. Maternal undernutrition changed the hepatic metabolic profile and affected the metabolic pathway involved in amino acid, glycerophospholipid, bile acid, purine, and saccharide metabolism in the fetuses, but not the kids. Additionally, maternal undernutrition increased the concentrations of GH and cortisol, elevated the hepatic glucose-6-phosphate dehydrogenase activity, and tended to decrease the hepatic glycogen content in the male kids. No alterations in these variables were observed in the female kids.ConclusionsMaternal undernutrition affects the metabolic status in a sex- and stage-specific manner by changing the metabolic profile, expression of genes involved in glucose homeostasis and enzyme activities in the liver of the fetuses. The changes in the hormone levels in the male fetuses and kids, but not the female offspring, represent a potential sign of metabolic programming.

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Section: Introductionmentioning

confidence: 99%

Evidence for liver energy metabolism programming in offspring subjected to intrauterine undernutrition during midgestation

et al. 2019

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“…As a follow-up to our previous studies 10,11,13 , we utilized baboons with an average age of 15 years (approximate human equivalent; 60 years), representing animals in or transitioning to the late stage of life, to investigate the long-term impact of MUN on the liver at the functional and molecular level. In the present study, we assessed clinical phenotypes of liver function by analyzing plasma changes in liver enzymes to identify functional hepatic deficits related to MUN in the aging offspring.…”

Section: Introductionmentioning

confidence: 99%

Perinatal maternal undernutrition in baboons modulates hepatic mitochondrial function but not metabolites in aging offspring

Adekunbi,

Yang,

Huber

et al. 2024

Preprint

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We previously demonstrated in baboons that maternal undernutrition (MUN), achieved by 70 % of control nutrition, impairs fetal liver function, but long-term changes associated with aging in this model remain unexplored. Here, we assessed clinical phenotypes of liver function, mitochondrial bioenergetics, and protein abundance in adult male and female baboons exposed to MUN during pregnancy and lactation and their control counterparts. Plasma liver enzymes were assessed enzymatically. Liver glycogen, choline, and lipid concentrations were quantified by magnetic resonance spectroscopy. Mitochondrial respiration in primary hepatocytes under standard culture conditions and in response to metabolic (1 mM glucose) and oxidative (100 uM H2O2) stress were assessed with Seahorse XFe96. Hepatocyte mitochondrial membrane potential (MMP) and protein abundance were determined by tetramethylrhodamine ethyl ester staining and immunoblotting, respectively. Liver enzymes and metabolite concentrations were largely unaffected by MUN, except for higher aspartate aminotransferase levels in MUN offspring when male and female data were combined. Oxygen consumption rate, extracellular acidification rate, and MMP were significantly higher in male MUN offspring relative to control animals under standard culture. However, in females, cellular respiration was similar in control and MUN offspring. In response to low glucose challenge, only control male hepatocytes were resistant to low glucose-stimulated increase in basal and ATP-linked respiration. H2O2 did not affect hepatocyte mitochondrial respiration. Protein markers of mitochondrial respiratory chain subunits, biogenesis, dynamics, and antioxidant enzymes were unchanged. Male-specific increases in mitochondrial bioenergetics in MUN offspring may be associated with increased energy demand in these animals. The similarity in systemic liver parameters suggests that changes in hepatocyte bioenergetics capacity precede detectable circulatory hepatic defects in MUN offspring and that the mitochondria may be an orchestrator of liver programming outcome.

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“…We have developed a well‐characterized baboon model of moderate MNR (70% of chow fed to controls, CON) during pregnancy, resulting in IUGR and fetal renal, 15 , 16 , 17 , 18 cardiovascular, 19 metabolic, 20 , 21 , 22 hepatic, 23 , 24 and neural 25 phenotypes in female and male offspring. 18 , 25 , 26 By 0.5 gestation (G), the fetal kidney showed decreased tubule length and down‐regulation of genes directing kidney branching morphogenesis 15 and mTOR nutrient sensing.…”

Section: Introductionmentioning

confidence: 99%

Postnatal persistence of nonhuman primate sex‐dependent renal structural and molecular changes programmed by intrauterine growth restriction

Bishop

Spradling-Reeves

Shade

et al. 2022

J of Medical Primatology

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Background Poor nutrition during fetal development programs postnatal kidney function. Understanding postnatal consequences in nonhuman primates (NHP) is important for translation to our understanding the impact on human kidney function and disease risk. We hypothesized that intrauterine growth restriction (IUGR) in NHP persists postnatally, with potential molecular mechanisms revealed by Western‐type diet challenge. Methods IUGR juvenile baboons were fed a 7‐week Western diet, with kidney biopsies, blood, and urine collected before and after challenge. Transcriptomics and metabolomics were used to analyze biosamples. Results Pre‐challenge IUGR kidney transcriptome and urine metabolome differed from controls. Post‐challenge, sex and diet‐specific responses in urine metabolite and renal signaling pathways were observed. Dysregulated mTOR signaling persisted postnatally in female pre‐challenge. Post‐challenge IUGR male response showed uncoordinated signaling suggesting proximal tubule injury. Conclusion Fetal undernutrition impacts juvenile offspring kidneys at the molecular level suggesting early‐onset blood pressure dysregulation.

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Influence of moderate maternal nutrition restriction on the fetal baboon metabolome at 0.5 and 0.9 gestation

Abstract: Background and Aims

Cited by 11 publications

References 37 publications

Evidence for liver energy metabolism programming in offspring subjected to intrauterine undernutrition during midgestation

Evidence for liver energy metabolism programming in offspring subjected to intrauterine undernutrition during midgestation

Perinatal maternal undernutrition in baboons modulates hepatic mitochondrial function but not metabolites in aging offspring

Postnatal persistence of nonhuman primate sex‐dependent renal structural and molecular changes programmed by intrauterine growth restriction

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