Postnatal Growth Restriction in Mice Alters Cardiac Protein Composition and Leads to Functional Impairment in Adulthood

Visker, Joseph R.; Dangott, Lawrence J.; Leszczynski, Eric C.; Ferguson, David P.

doi:10.3390/ijms21249459

Cited by 4 publications

(11 citation statements)

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“…Today, a number of epidemiological studies and animal model studies suggest that environmental factors in embryonic, fetal, neonatal, and early childhood periods are associated with health and disease in adulthood and old age, including the risk of developing chronic diseases, supporting the DOHaD theory [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. For example, in cases of food deprivation during pregnancy, the fetus acquires an energy-saving constitution in anticipation of the environment after birth, in which nutrient intake may be insufficient [ 78 ].…”

Section: Dohad Theorymentioning

confidence: 99%

Mitochondrial DNA Copy Number and Developmental Origins of Health and Disease (DOHaD)

Fukunaga

2021

IJMS

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Mitochondrial dysfunction is known to contribute to mitochondrial diseases, as well as to a variety of aging-based pathologies. Mitochondria have their own genomes (mitochondrial DNA (mtDNA)) and the abnormalities, such as point mutations, deletions, and copy number variations, are involved in mitochondrial dysfunction. In recent years, several epidemiological studies and animal experiments have supported the Developmental Origin of Health and Disease (DOHaD) theory, which states that the environment during fetal life influences the predisposition to disease and the risk of morbidity in adulthood. Mitochondria play a central role in energy production, as well as in various cellular functions, such as apoptosis, lipid metabolism, and calcium metabolism. In terms of the DOHaD theory, mtDNA copy number may be a mediator of health and disease. This paper summarizes the results of recent epidemiological studies on the relationship between environmental factors and mtDNA copy number during pregnancy from the perspective of DOHaD theory. The results of these studies suggest a hypothesis that mtDNA copy number may reflect environmental influences during fetal life and possibly serve as a surrogate marker of health risks in adulthood.

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Section: Dohad Theorymentioning

confidence: 99%

Mitochondrial DNA Copy Number and Developmental Origins of Health and Disease (DOHaD)

Fukunaga

2021

IJMS

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“…show that in the heart the mitochondrial content of the PGR mice is reduced by 26.3%, which may contribute to cardiac pathology (reduced LV mass, reduced cardiac output and increased isovolumetric contraction/relaxation time) as evident from studies using identical mice and experimental design (Ferguson et al, 2019;Pendergrast et al, 2020;Visker et al, 2018Visker et al, , 2020. Additionally, in support of previous DOHaD research, tibia lengths of PGR mice were reduced at PN22 and PN80, which typically associates with less overall growth and is suggestive of impaired lean tissue growth (Fiorotto et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…PGR mouse hearts are reported to have reduced levels of antioxidant enzymes, mainly PRDX6, which may indicate impairments to cytosolic and mitochondrial ROS handling (Visker et al, 2020).…”

Section: High-resolution Respirometry and Fluorimetrymentioning

confidence: 99%

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Postnatal growth restriction alters myocardial mitochondrial energetics in mice

Visker,

Leszczynski,

Wellette‐Hunsucker

et al. 2024

Experimental Physiology

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Postnatal growth restriction (PGR) can increase the risk of cardiovascular disease (CVD) potentially due to impairments in oxidative phosphorylation (OxPhos) within cardiomyocyte mitochondria. The purpose of this investigation was to determine if PGR impairs cardiac metabolism, specifically OxPhos. FVB (Friend Virus B‐type) mice were fed a normal‐protein (NP: 20% protein), or low‐protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce ∼20% less milk, and pups nursed by LP dams experience reduced growth into adulthood as compared to pups nursed by NP dams. At birth (PN1), pups born to dams fed the NP diet were transferred to LP dams (PGR group) or a different NP dam (control group: CON). At weaning (PN21), all mice were fed the NP diet. At PN22 and PN80, mitochondria were isolated for respirometry (oxygen consumption rate, ) and fluorimetry (reactive oxygen species emission, ) analysis measured as baseline respiration (LEAK) and with saturating ADP (OxPhos). Western blotting at PN22 and PN80 determined protein abundance of uncoupling protein 3, peroxiredoxin‐6, voltage‐dependent anion channel and adenine nucleotide translocator 1 to provide further insight into mitochondrial function. ANOVAs with the main effects of diet, sex and age with α‐level of 0.05 was set a priori. Overall, PGR (7.8 ± 1.1) had significant (P = 0.01) reductions in respiratory control in complex I when compared to CON (8.9 ± 1.0). In general, our results show that PGR led to higher electron leakage in the form of free radical production and reactive oxygen species emission. No significant diet effects were found in protein abundance. The observed reduced respiratory control and increased ROS emission in PGR mice may increase risk for CVD in mice.

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“…Nutritive model for growth restriction in mice. A reliable and validated nutritive model was used to induce early life GR (17)(18)(19)(20). Friend Virus B (Charles River Laboratories, Wilmington, MA) mice were fed isocaloric diets that were either a semi-purified normal protein (NP) diet (20 kcal% protein: D17041407, Research Diets, New Brunswick, NJ) based on AIN93G or a low-protein diet (LP; 8 kcal% protein) (20) 2 wk before mating (Fig.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Downhill Running on Quadriceps Muscle in Growth-Restricted Mice

Wellette-Hunsucker¹,

Leszczynski

Visker³

et al. 2023

Medicine &Amp; Science in Sports &Amp; Exercise

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Introduction Growth-restriction (GR) reduces ribosome abundance and skeletal muscle mass in mice. A reduction in skeletal muscle mass increases the risk of frailty and is associated with high morbidity and mortality rates. As eccentric type exercise increases muscle mass, this investigation aimed to determine if eccentric loading of skeletal muscle via downhill running (DHR) increased muscle mass in GR mice. Methods Mice were growth-restricted either gestational undernutrition (GUN: n = 8 litters), postnatal undernutrition (PUN: n = 8 litters) or were not restricted (CON: n = 8 litters) via a validated cross-fostering nutritive model. On postnatal day (PN) 21, all mice were weaned to a healthy diet, isolating the period of GR to early life as seen in humans. At PN45, mice were assigned to either a downhill running (DHR, CON n = 4 litters, GUN n = 4 litters, PUN n = 4 litters) or sedentary (SED, CON n = 4 litters, GUN n = 4 litters, PUN n = 4 litters) group. DHR (16% decline: 18 m/min) was performed in 30-minute bouts, three times per week, for 12 weeks on a rodent treadmill. At PN129, the quadriceps femoris was dissected and evaluated for mass, myofiber size and type, and molecular markers of growth. Results Following training, CON-DHR mice having larger cells than CON-SED, GUN-SED, PUN-SED, and PUN-DHR mice (p < 0.05). The PUN group (as compared to CON) had reduced body mass (p < 0.001), UBF abundance (p = 0.012), phosphor-mTOR (p < 0.001), and quadriceps mass (p = 0.02). The GUN and PUN groups had increased MuRF1 abundance (p < 0.001) compared to CON (p < 0.001). Conclusions The blunted response to training suggests GR mice may have anabolic resistance when exposed to eccentric type exercise.

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Postnatal Growth Restriction in Mice Alters Cardiac Protein Composition and Leads to Functional Impairment in Adulthood

Cited by 4 publications

References 96 publications

Mitochondrial DNA Copy Number and Developmental Origins of Health and Disease (DOHaD)

Mitochondrial DNA Copy Number and Developmental Origins of Health and Disease (DOHaD)

Postnatal growth restriction alters myocardial mitochondrial energetics in mice

The Effect of Downhill Running on Quadriceps Muscle in Growth-Restricted Mice

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