title: Lipid overload during gestation and lactation can independently alter lipid homeostasis in offspring and promote metabolic impairment after new challenge to high-fat diet.
abstract: BACKGROUND
  Nutritional status in early life is critically involved in the metabolic phenotype of offspring. However the changes triggered by maternal consumption of high-fat diet (HFD) in pre- or postnatal period should be better understood. Here we evaluated whether maternal HFD consumption during gestation and lactation could differently affect liver miR-122 and miR-370 expression leading to metabolic damages observed in offspring. Moreover, we investigate whether early overnutrition program offspring to more harmful response to HFD in later life.
  
  
  METHODS
  Female mice were fed either a standard chow (SC) diet or a HFD three weeks before and during mating, gestation and/or lactation. Offspring were evaluated on the delivery day (d0), in a cross-fostering model at day 28 (d28) and in adult life, after a re-challenge with a HFD (d82).
  
  
  RESULTS
  In vitro analysis using liver cell line showed that palmitate could induced decrease in miR-122 and increase in miR-370 expression. Newborn pups (d0) from obese dams showed a decrease in lipid oxidation markers (Cpt1aandAcadvl), an increase in triacylglycerol synthesis markers (AgpatandGpam), as well as lower miR-122 and higher miR-370 hepatic content that was inversely correlated to maternal serum NEFA and TAG. Pups fostered to SC dams presented an increase in body weight andAgpat/Gpamexpression at d28 compared to pups fostered to HFD dams and an inverse correlation was observed between miR-122 hepatic expression and offspring serum TAG. In adult life (d82), the reintroduction of HFD resulted in higher body weight gain and hepatic lipid content. These effects were accompanied by impairment in lipid and glucose metabolism, demonstrated by reducedCpt1a/Acadvland increasedAgpat/Gpamexpression, lower glucose tolerance and insulin sensitivity.
  
  
  CONCLUSIONS
  Our data suggest that both gestational and lactation overnutrition results in metabolic changes that can permanently alter lipid homeostasis in offspring. The presence of fatty acids in maternal blood and milk seem to be responsible for modulating the expression ofmiR-122andmiR-370, which are involved in liver metabolism. These alterations significantly increase susceptibility to obesity and ectopic lipid accumulation and lead to a more harmful response to HFD in offspring.
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo Brazil.
authors.forename: Laís Angélica
authors.initials: LA
authors.lastname: de Paula Simino
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo Brazil.
authors.forename: Thaís
authors.initials: T
authors.lastname: de Fante
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: Figueiredo Fontana
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Oliveira Borges
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo Brazil.
authors.forename: Márcio Alberto
authors.initials: MA
authors.lastname: Torsoni
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo Brazil.
authors.forename: Marciane
authors.initials: M
authors.lastname: Milanski
authors.affiliation: Laboratory of Cell Signaling, Faculty of Medical Sciences, University Of Campinas - UNICAMP, Campinas, São Paulo Brazil.
authors.forename: Lício Augusto
authors.initials: LA
authors.lastname: Velloso
authors.affiliation: Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Souza Torsoni
keywords: Maternal obesity; Metabolic programming; NAFLD; microRNAs