title: The insulin-signaling pathway of the pancreatic islet is impaired in adult mice offspring of mothers fed a high-fat diet.
abstract: OBJECTIVE
  Mothers fed a high-fat (HF) diet can cause different adverse alterations in their offspring. The study aimed to verify the pancreatic islet structure and insulin-signaling pathway in adulthood of offspring of mothers fed a HF diet during the pregnancy.
  
  
  METHODS
  Female mice (mothers) were randomly assigned to receive either standard chow (Mo-SC) or a HF diet (Mo-HF) ad libitum. After 2 mo on the experimental diets, 3-mo-old female mice were mated with male C57 BL/6 mice that were fed a SC diet. The male offspring was evaluated at 6 mo old.
  
  
  RESULTS
  At 6 mo of age, Mo-HF offspring had an increment in body mass and adiposity, hypercholesterolemia, and hypertriacylglycerolemia, higher levels of insulin, and leptin with a concomitant decrease in adiponectin levels. In the islet, we observed an alteration in the structure characterized by the migration of some alpha cells from the edge to the core of the islet in association with an increase in the masses of the islet, beta cell, and alpha cell, featuring a pancreatic islet remodeling. Additionally, the Mo-HF offspring demonstrated a decrease in IRS1, PI3 k p-Akt, Pd-1, and Glut2 protein expressions compared to Mo-SC offspring. However, an increase was observed in FOXO1 and insulin protein expressions in Mo-HF offspring compared to Mo-SC offspring.
  
  
  CONCLUSIONS
  The present study demonstrated that a maternal HF diet is responsible for remodeling the islet structure coupled with an adverse carbohydrate metabolism and impairment of the insulin-signaling pathway in adult male mice offspring.
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Isabele
authors.initials: I
authors.lastname: Bringhenti
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Ornellas
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: Marciaguila@gmail.com.
authors.forename: Marcia Barbosa
authors.initials: MB
authors.lastname: Aguila
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D007328:Insulin
keywords: Fetal programming; Insulin resistance; Insulin signaling; Mice; Pancreatic islet