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

PLoS One. 2014 Aug 13;9(8):e104896. doi: 10.1371/journal.pone.0104896. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / metabolism
  • Age Factors
  • Animals
  • Blotting, Western
  • Body Temperature
  • Body Weight
  • Calorimetry, Indirect
  • DNA Primers / genetics
  • Diet, High-Fat / adverse effects
  • Eating
  • Energy Metabolism / genetics*
  • Female
  • Lactation / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mitochondria / physiology*
  • Obesity / metabolism
  • Obesity / prevention & control*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Protein Deficiency / physiopathology*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers

Grants and funding

The study was funded by a grant from ANR (French Agency for Research, Epidiabesity). The Centre National pour la Recherche Scientifique (CNRS) provided salaries for CJ and PF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.