Short-term moderate diet restriction in adulthood can reverse oxidative, cardiovascular and metabolic alterations induced by postnatal overfeeding in mice

Na Li,Catherine Vergely,Pauline Chollet,Charles Guenancia,Luc Rochette,Olivier Hachet,Lucie Desmoulins,Corinne Leloup,Eve Rigal

doi:10.1038/srep30817

Abstract

We aimed to determine whether moderate diet restriction could restore cardiac, oxidative and metabolic alterations induced by postnatal overfeeding (PNOF). Litters of C57BL/6 male mice were either maintained at 9 (normal litter, NL), or reduced to 3 (small litter, SL) in order to induce PNOF. At 6 months, half of the NL and SL mice were subjected to 20% calorie-restriction (CR: NLCR, SLCR) for one month, while the other half continued to eat ad libitum (AL: NLAL, SLAL). Six-month old SL mice presented overweight, fat accumulation, hyperleptinemia, glucose intolerance, insulin resistance, increased cardiac ROS production and decreased left ventricular ejection fraction (LVEF). After CR, SL mice body weight was normalized; however, their fat mass and leptinemia were not decreased, glucose metabolism was improved and LVEF was increased. In SL mice, CR increased the cardiac mitochondrial respiratory rate and decreased cardiac ROS production. Hearts from SLCR mice showed better recovery and smaller postischemic infarct size. Intriguingly, no difference was observed between NLAL and NLCR mice for most of the parameters investigated. Short-term moderate CR not only normalized body weight in SL mice but also improved metabolic programming and reversed oxidative and cardiac dysfunction induced by PNOF.

Highlights

To cite this version: Na Li, Charles Guenancia, Eve Rigal, Olivier Hachet, Pauline Chollet, et al
Clinical and experimental data from animal models have clearly demonstrated that altered nutritional experiences during critical periods of development are an important factor in the etiology of obesity and related metabolic diseases
Previous research at our laboratory indicated that postnatal overnutrition induced metabolic symptoms, and early changes in heart gene expression that may have a long-term effect on cardiovascular function and heart structure in adult rodents, and may have a deleterious impact on myocardial recovery after ischemic injury[10]

Summary

Introduction

To cite this version: Na Li, Charles Guenancia, Eve Rigal, Olivier Hachet, Pauline Chollet, et al. Short-term moderate diet restriction in adulthood can reverse oxidative, cardiovascular and metabolic alterations induced by postnatal overfeeding in mice. HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. We aimed to determine whether moderate diet restriction could restore cardiac, oxidative and metabolic alterations induced by postnatal overfeeding (PNOF). After CR, SL mice body weight was normalized; their fat mass and leptinemia were not decreased, glucose metabolism was improved and LVEF was increased. Short-term moderate CR normalized body weight in SL mice and improved metabolic programming and reversed oxidative and cardiac dysfunction induced by PNOF. Due to genomic plasticity, the neonatal period is critical for the orientation of phenotypic features in adulthood, since epigenetic modifications may impact gene expression and influence the development of chronic disease

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