title: Sex-dependent programming of glucose and fatty acid metabolism in mouse offspring by maternal protein restriction.
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.
authors.affiliation: Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Esther M E
authors.initials: EM
authors.lastname: van Straten
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bloks
authors.forename: Theo H
authors.initials: TH
authors.lastname: van Dijk
authors.forename: Julius F W
authors.initials: JF
authors.lastname: Baller
authors.forename: Nicolette C A
authors.initials: NC
authors.lastname: Huijkman
authors.forename: Irma
authors.initials: I
authors.lastname: Kuipers
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.forename: Torsten
authors.initials: T
authors.lastname: Plösch
mesh_terms: D000328:Adult; D000818:Animals; D059305:Diet, High-Fat; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena; D012737:Sex Factors
chemical_list: D005227:Fatty Acids; D005947:Glucose