Perinatal protein malnutrition affects mitochondrial function in adult and results in a resistance to high fat diet-induced obesity.

Céline Jousse,Pierre Fafournoux,Laurent Parry,Patrick Even,Alain Bruhat,Béatrice Morio,Julien Averous,Jacques Mallet,Yuki Muranishi,Cédric Chaveroux,Valérie Carraro,Anne-Catherine Maurin,Christophe Montaurier,Jean-Marie Launay

doi:10.1371/journal.pone.0104896

Abstract

Epidemiological findings indicate that transient environmental influences during perinatal life, especially nutrition, may have deleterious heritable health effects lasting for the entire life. Indeed, the fetal organism develops specific adaptations that permanently change its physiology/metabolism and that persist even in the absence of the stimulus that initiated them. This process is termed “nutritional programming”. We previously demonstrated that mothers fed a Low-Protein-Diet (LPD) during gestation and lactation give birth to F1-LPD animals presenting metabolic consequences that are different from those observed when the nutritional stress is applied during gestation only. Compared to control mice, adult F1-LPD animals have a lower body weight and exhibit a higher food intake suggesting that maternal protein under-nutrition during gestation and lactation affects the energy metabolism of F1-LPD offspring. In this study, we investigated the origin of this apparent energy wasting process in F1-LPD and demonstrated that minimal energy expenditure is increased, due to both an increased mitochondrial function in skeletal muscle and an increased mitochondrial density in White Adipose Tissue. Importantly, F1-LPD mice are protected against high-fat-diet-induced obesity. Clearly, different paradigms of exposure to malnutrition may be associated with differences in energy expenditure, food intake, weight and different susceptibilities to various symptoms associated with metabolic syndrome. Taken together these results demonstrate that intra-uterine environment is a major contributor to the future of individuals and disturbance at a critical period of development may compromise their health. Consequently, understanding the molecular mechanisms may give access to useful knowledge regarding the onset of metabolic diseases.

Highlights

Metabolic diseases, including obesity and Type II Diabetes Mellitus (T2DM) are among the leading causes of disability in industrialized countries
We investigated the origin of this apparent energy wasting process in F1-LPD mice and demonstrated that minimal energy expenditure is increased in F1-LPD animals, due to both an increased mitochondrial function in skeletal muscle and an increased mitochondrial density in White Adipose Tissue
Metabolic diseases have multiple origins, including genetic and environmental factors and their patho-physiological characteristics are diverse and complex. Transient environmental influences, such as a nutritional stress during perinatal life, may have deleterious long lasting health effects that may last for the entire life of affected individuals [1], suggesting a fetal origin of metabolic diseases, a field that have been of growing interest in the last years

Summary

Introduction

Metabolic diseases, including obesity and Type II Diabetes Mellitus (T2DM) are among the leading causes of disability in industrialized countries. Extensive epidemiological findings indicate that a key feature characteristic of these diseases is that transient environmental influences during perinatal life may have deleterious heritable health effects lasting for the entire life [1]. Among these environmental factors, nutrition plays a major role especially during critical windows of development. The fetal organism is able to respond to nutritional stresses by specific adaptations at the cellular and molecular levels that permanently change the physiology and the metabolism of the organism and persist even in the absence of the stress/stimulus that initiated them.

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Conclusion