Early life undernutrition reduces maximum treadmill running capacity in adulthood in mice

Pendergrast, Logan A.; Leszczynski, Eric C.; Visker, Joseph R.; Triplett, Ashley; Ferguson, David P.

doi:10.1139/apnm-2019-0023

Cited by 9 publications

(19 citation statements)

References 53 publications

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“…The PGR group had impairments in global cardiac function and mass (LV mass, stroke volume, cardiac output, myocardial performance index [MPI]), and diminished diastolic/systolic function (prolonged isovolumetric contraction/relaxation) in adulthood. These findings support the existing DOHaD literature, which has shown that PGR in mice impairs functional capacity of the heart, calcium flux, and exercise capacity, leading to an increased risk for CVD and mortality in adulthood [12,15,17,23,24,[28][29][30][31][32][33][34][35][36][37].…”

Section: Discussionsupporting

confidence: 90%

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

Visker

Dangott

Leszczynski

et al. 2020

IJMS

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Postnatal growth restriction (PGR) increases the risk for cardiovascular disease (CVD) in adulthood, yet there is minimal mechanistic rationale for the observed pathology. The purpose of this study was to identify proteomic differences in hearts of growth-restricted and unrestricted mice, and propose mechanisms related to impairment in adulthood. Friend leukemia virus B (FVB) mouse dams were fed a control (CON: 20% protein), or low-protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce 20% less milk, inducing growth restriction. At birth (postnatal; PN1), pups born to dams fed the CON diet were switched to LP dams (PGR group) or a different CON dam. At PN21, a sub-cohort of CON (n = 3 males; n = 3 females) and PGR (n = 3 males; n = 3 females) were euthanized and their proteome analyzed by two-dimensional differential in-gel electrophoresis (2D DIGE) and mass spectroscopy. Western blotting and silver nitrate staining confirmed 2D DIGE results. Littermates (CON: n = 4 males and n = 4 females; PGR: n = 4 males and n = 4 females) were weaned to the CON diet. At PN77, echocardiography measured cardiac function. At PN80, hearts were removed for western blotting to determine if differences persisted into adulthood. 2D DIGE and western blot confirmation indicated PGR had reductions in p57kip2, Titin (Ttn), and Collagen (Col). At PN77, PGR had impaired cardiac function as measured by echocardiography. At PN80, western blots of p57kip2 showed protein abundance recovered from PN21. PN80 silver staining of large molecular weight proteins (Ttn and Col) was reduced in PGR. PGR reduces cell cycle activity at PN21, which is recovered in adulthood. However, collagen fiber networks are altered into adulthood.

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Section: Discussionsupporting

confidence: 90%

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

Visker

Dangott

Leszczynski

et al. 2020

IJMS

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“…Starting at PN7, PUN pups displayed growth stunting and were 18% smaller ( P < 0.001) than the CON and GUN mice into adulthood. These observations are consistent with the literature (6,9,11,16). At completion of the investigation (PN70) female mice were smaller than male mice within each diet group (Fig.…”

Section: Resultssupporting

confidence: 94%

“…Cardiac parameters mirrored existing literature (11) with males having a larger left ventricular (LV) volume during diastole ( P = 0.030; Table 1), stroke volume ( P = 0.0105; Table 2), and cardiac output ( P = 0.0129; Table 2) compared with female mice. Females showed a larger LV-anterior wall diameter during diastole ( P = 0.0347; Table 2) and LV-posterior wall diameter during diastole ( P = 0.0125; Table 2).…”

Section: Resultssupporting

confidence: 78%

“…Diaphragm, extensor digitorum longus (EDL), and soleus were extracted for skeletal muscle histology by positioning the samples in optimal cutting temperature compound (O.C.T.) and frozen in liquid nitrogen cooled isobutane as previously described (11). Skeletal muscle samples were sectioned into 5-μm slices using a cryostat microtome (Leica, Wetzlar, Germany) and placed onto glass microscope slides and stored at −20°C until histological staining.…”

Section: Methodsmentioning

confidence: 99%

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Physical Activity Engagement Worsens Health Outcomes and Limits Exercise Capacity in Growth-restricted Mice

Ferguson

Leszczynski

McPeek

et al. 2021

Medicine &Amp; Science in Sports &Amp; Exercise

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Introduction: A total of 161 million children a year are growth restricted, leading to a 47% increased risk of chronic disease in adulthood. Physical activity (PA) reduces the risk of mortality from chronic disease. The purpose of the present investigation was to determine the effect of a PA intervention (wheel running) on cardiac and skeletal muscle capacities in gestational (GUN) and postnatal (PUN) growth-restricted mice as compared with nonrestricted controls (CON). Methods: A low-protein cross-fostering FVB mouse model was used to induce growth restriction during gestation and the first 21 d of postnatal life. Mouse pups were recovered on a healthy diet until mature and provided wheel access for 3 wk. At completion of the PA intervention, mice underwent maximal exercise testing on a treadmill, echocardiography, and skeletal muscle histology. Results: After the PA intervention, CON mice had a 45% improvement in maximal exercise capacity (P = 0.0390) because of cardiac and skeletal muscle adaptations, but GUN and PUN mice did not. Alarmingly, PUN female mice exposed to wheels had 11.45% lower left ventricular volume (P = 0.0540) and 18% lower left ventricle area (P = 0.0585), with blood flow velocities indicative of cardiac fibrosis (GUN had elevated isovolumetric contraction time P = 0.0374; GUN females and PUN males had longer isovolumetric relaxation time P = 0.0703). PUN male mice had mixed skeletal muscle responses with an oxidative shift in the diaphragm (P = 0.0162) but a glycolytic shift in the extensor digitorum longus (P = 0.0647). PUN female mice had a glycolytic shift in the soleus after wheel running. Conclusions: Unexpectedly, growth-restricted mice were nonresponders to a PA intervention and displayed negative cardiac outcomes.

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“…On the contrary, the consequences of early life nutrition restriction, especially protein restriction, are far-reaching and influential. For instance, human aging cohort studies have shown that low birth weight due to malnutrition during pregnancy is strongly associated with decreased muscle volume and strength in later life [ 5 , 6 , 7 ]. Besides general overnutrition or undernutrition, overconsumption or deficiency of essential nutrients also stunts organ and tissue development, resulting in later-life risks [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome and Methylome Profiling in Rat Skeletal Muscle: Impact of Post-Weaning Protein Restriction

Hasegawa

Nakai

et al. 2022

IJMS

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Skeletal muscle is programmable, and early-life nutritional stimuli may form epigenetic memory in the skeletal muscle, thus impacting adult muscle function, aging, and longevity. In the present study, we designed a one-month protein restriction model using post-weaning rats, followed by a two-month rebound feeding, to investigate how early-life protein restriction affects overall body growth and muscle development and whether these influences could be corrected by rebound feeding. We observed comprehensive alterations immediately after protein restriction, including retarded growth, altered biochemical indices, and disturbed hormone secretion. Transcriptome profiling of the gastrocnemius muscle followed by gene ontology analyses revealed that “myogenic differentiation functions” were upregulated, while “protein catabolism” was downregulated as a compensatory mechanism, with enhanced endoplasmic reticulum stress and undesired apoptosis. Furthermore, methylome profiling of the gastrocnemius muscle showed that protein restriction altered the methylation of apoptotic and hormone secretion-related genes. Although most of the alterations were reversed after rebound feeding, 17 genes, most of which play roles during muscle development, remained altered at the transcriptional level. In summary, early-life protein restriction may undermine muscle function in the long term and affect skeletal muscle development at the both transcriptional and methylation levels, which may hazard future muscle health.

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Early life undernutrition reduces maximum treadmill running capacity in adulthood in mice

Cited by 9 publications

References 53 publications

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

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

Physical Activity Engagement Worsens Health Outcomes and Limits Exercise Capacity in Growth-restricted Mice

Transcriptome and Methylome Profiling in Rat Skeletal Muscle: Impact of Post-Weaning Protein Restriction

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