title: Pregestational maternal obesity impairs endocrine pancreas in male F1 and F2 progeny.
abstract: OBJECTIVE
  The aim of this study was to evaluate the effects of maternal obesity on pancreas structure and carbohydrate metabolism in early adult life, focusing on the F1 and F2 generations after F0 maternal pregestational, gestation, and lactation high-fat diet (HF).
  
  
  METHODS
  C57 BL/6 female mice (F0) were fed standard chow (SC) or an HF diet for 8 wk before mating and during the gestation and lactation periods to provide the F1 generation (F1-SC and F1-HF). At 3 mo old, F1 females were mated to produce the F2 generation (F2-SC and F2-HF). The male offspring from all groups were evaluated at 3 mo old.
  
  
  RESULTS
  F0-HF and F1-HF dams were overweight before gestation and had a higher body mass gain and energy intake during gestation, although only F0-HF dams presented pregestational hyperglycemia. The F1-HF offspring had higher body mass, energy intake, fasting glucose levels, and were glucose intolerant compared with F1-SC offspring. These parameters were not significantly altered in F2-HF offspring. Both F1-HF and F2-HF offspring showed hyperinsulinemia, hyperleptinemia, decreased adiponectin levels, increased pancreatic mass, and islet volume density with elevated α- and β-cell mass, hypertrophied islet characterized by an altered distribution of α- and β-cells and weak pancreatic-duodenal homeobox (Pdx)1 immunoreactivity.
  
  
  CONCLUSIONS
  Maternal HF diet consumed during the preconception period and throughout the gestation and lactation periods in mice promotes metabolism and pancreatic programming in F1 and F2 male offspring, implying intergenerational effects.
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors.forename: Francielle
authors.initials: F
authors.lastname: Graus-Nunes
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors.forename: Eliete
authors.initials: E
authors.lastname: Dalla Corte Frantz
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors.forename: Wilian Rodrigues
authors.initials: WR
authors.lastname: Lannes
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors.forename: Mariel Caroline
authors.initials: MC
authors.lastname: da Silva Menezes
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil. Electronic address: souzamello.uerj@gmail.com.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Souza-Mello
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D002149:Energy Intake; D005260:Female; D006943:Hyperglycemia / Q000473:pathology; D006946:Hyperinsulinism / Q000473:pathology; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000503:physiopathology*; D007774:Lactation / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000473:pathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin
keywords: High-fat diet; Hyperinsulinemia; Intergenerational effects; Maternal obesity; Pancreatic islet