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

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

doi:10.1016/j.genm.2012.01.004

« BackGender Medicine: The Journal for the Study of Sex & Gender Differences

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

Esther M.E. van Straten, PhD
- Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Vincent W. Bloks
- Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Theo H. van Dijk, PhD
- Department of Laboratory Medicine, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Julius F.W. Baller
- Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Nicolette C.A. Huijkman
- Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Irma Kuipers, PhD
- Department of Experimental Cardiology, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Henkjan J. Verkade, MD, PhD
- Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Torsten Plösch, PhD
- Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
- Address correspondence to: Torsten Plösch, Department of Pediatrics, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

Accepted 9 January 2012. published online 23 February 2012.
Corrected Proof

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.

Key words: developmental origins hypothesis , glucose metabolism , imprinting , metabolic programming , sex specificity