Sex-Dependent Programming of Glucose and Fatty Acid Metabolism in Mouse Offspring by Maternal Protein Restriction

Esther M. E. van Straten, Vincent W. Bloks, Theo H. van Dijk, Julius F. W. Baller, Nicolette C. A. Huijkman, Irma Kuipers, Henkjan J. Verkade, Torsten Plosch*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

Background: Nutritional conditions during fetal life influence the risk of the development of metabolic syndrome and cardiovascular diseases in adult life (metabolic programming). Impaired glucose tolerance and dysregulated fatty acid metabolism are hallmarks of metabolic syndrome.

Objective: We aimed to establish a mouse model of metabolic programming focusing on the sex-specific effects of a maternal low-protein diet during gestation on glucose and lipid metabolism in the adult offspring.

Methods: Pregnant C57BL/6 mice received a control or a low-protein diet (18% vs 9% casein) throughout gestation. Male and female offspring received a low-fat or a high-fat diet from 6 to 22 weeks of age.

Results: Maternal low-protein diet during gestation led to deteriorated insulin sensitivity on high-fat feeding in female offspring, as determined by biochemical and microarray analyses. Female offspring of control diet fed dams were relatively resistant to high-fat diet induced metabolic dysregulation. In contrast, maternal low-protein diet did not specifically affect the metabolic parameters addressed in male offspring. In males, the high-fat diet led to insulin insensitivity regardless of the diet of the dam.

Conclusions: Our findings show that fetal malnutrition has a limited impact on male mouse offspring, yet it does influence the metabolic response to a high-fat diet in females. These findings may have implications for future early diagnostics in metabolic syndrome and for the development of sex-specific treatment regimens. (Gend Med. 2012;9:166-179) (C) 2012 Elsevier HS Journals, Inc. All rights reserved.

Original languageEnglish
Pages (from-to)166-179
Number of pages14
JournalGender medicine
Volume9
Issue number3
DOIs
Publication statusPublished - Jun-2012

Keywords

  • developmental origins hypothesis
  • glucose metabolism
  • imprinting
  • metabolic programming
  • sex specificity
  • HEPATIC INSULIN-RESISTANCE
  • DIETARY-PROTEIN
  • BLOOD-PRESSURE
  • LIPID-METABOLISM
  • ADULT DISEASE
  • FETAL ORIGINS
  • PREGNANT RATS
  • MICE
  • HYPERTENSION
  • EXPRESSION

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