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Perinatal nutrient restriction induces long-lasting alterations in the circadian expression pattern of genes regulating food intake and energy metabolism

International Journal of Obesity volume 35, pages 990–1000 (2011)Cite this article

Subjects

Abstract

Objective:

Several lines of evidence indicate that nutrient restriction during perinatal development sensitizes the offspring to the development of obesity, insulin resistance and cardiovascular disease in adulthood via the programming of hyperphagia and reduced energy expenditure. Given the link between the circadian clock and energy metabolism, and the resetting action of food on the circadian clock, in this study, we have investigated whether perinatal undernutrition affects the circadian expression rhythms of genes regulating food intake in the hypothalamus and energy metabolism in the liver.

Design:

Pregnant Sprague-Dawley rats were fed ad libitum either a control (20% protein) or a low-protein (8% protein) diet throughout pregnancy and lactation. At weaning, pups received a standard diet and at 17 and 35 days of age, their daily patterns of gene expression were analyzed by real-time quantitative PCR experiments.

Results:

17-day-old pups exposed to perinatal undernutrition exhibited significant alterations in the circadian expression profile of the transcripts encoding diverse genes regulating food intake, the metabolic enzymes fatty acid synthase and glucokinase as well as the clock genes BMAL1 and Period1. These effects persisted after weaning, were associated with hyperphagia and mirrored the results of the behavioral analysis of feeding. Thus, perinatally undernourished rats exhibited an increased hypothalamic expression of the orexigenic peptides agouti-related protein and neuropeptide Y. Conversely, the mRNA levels of the anorexigenic peptides pro-opiomelanocortin and cocaine and amphetamine-related transcripts were decreased.

Conclusion:

These observations indicate that the circadian clock undergoes nutritional programming. The programming of the circadian clock may contribute to the alterations in feeding and energy metabolism associated with malnutrition in early life, which might promote the development of metabolic disorders in adulthood.

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Acknowledgements

This work was supported by INRA through a Young Team Action and by l’Agence National de la Recherche (ANR-05-PNRA-009–02). R Orozco-Sólis is a doctoral fellow from the Mexican Consejo Nacional de Ciencia y Tecnología (CONACYT). S Lopes de Souza and Rhowena Matos are the recipient of a post-doctoral fellowship from La Region Pays de la Loire. The authors gratefully acknowledge M Jean Louis Lescure for his assistance with the care of the animals.

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Authors and Affiliations

  1. INRA, UMR1280 Physiologie des Adaptations Nutritionnelles, Nantes, France

    R Orozco-Solís, R J B Matos, I Grit, B Kaeffer & F Bolaños-Jiménez

  2. Université de Nantes, Nantes Atlantique Université, Nantes, France

    R Orozco-Solís, R J B Matos, I Grit, B Kaeffer & F Bolaños-Jiménez

  3. Departamento de Anatomia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil

    S Lopes de Souza

  4. Departamento de Nutriçao, Centro de Ciências da Saude, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil

    R Manhães de Castro

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  1. R Orozco-Solís
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Correspondence to F Bolaños-Jiménez.

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Orozco-Solís, R., Matos, R., Lopes de Souza, S. et al. Perinatal nutrient restriction induces long-lasting alterations in the circadian expression pattern of genes regulating food intake and energy metabolism. Int J Obes 35, 990–1000 (2011). https://doi.org/10.1038/ijo.2010.223

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