title: Methylglyoxal treatment in lactating mothers leads to type 2 diabetes phenotype in male rat offspring at adulthood.
abstract: OBJECTIVE
  Environmental and nutritional disorders during perinatal period cause metabolic dysfunction in the progeny and impair human health. Advanced glycation end products (AGEs) are primarily produced during metabolism of excess blood glucose, which is observed in diabetes. Methylglyoxal (MG) is a precursor for the generation of endogenous AGEs, which disturbs the metabolism. This work aimed to investigate whether the maternal MG treatment during lactation programs the progeny to metabolic dysfunction later in life.
  
  
  METHODS
  Female Wistar rats were divided into two groups: control group (C) treated with saline and MG group treated with MG (60 mg/kg/day) by gavage throughout the lactation period. Both mothers and offspring were fed a standard chow. At weaning, breast milk composition was analyzed and mothers euthanized for blood and tissue sample collections. At 90 days of age, offspring were submitted to glucose tolerance test (ivGTT) and euthanized for blood and tissue samples collection.
  
  
  RESULTS
  MG mothers showed increase in glucose and fructosamine levels; however, they showed low insulin levels and failure in β-cell function (p < 0.05). MG mothers also showed dyslipidemia (p < 0.05). Moreover, breast milk had elevated levels of glucose, triglycerides, cholesterol and fructosamine and low insulin (p < 0.05). Interestingly, MG offspring had increased body weight and adipose tissue at adulthood, and they also showed glucose intolerance and failure in β-cell function (p < 0.05). Besides, MG offspring showed dyslipidemia (p < 0.05) increasing cardiovascular diseases risk.
  
  
  CONCLUSIONS
  Maternal MG treatment negatively affects the male rat offspring, leading to type 2 diabetes and dyslipidemia in later life, possibly by changes in breast milk composition.
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Flávio Andrade
authors.initials: FA
authors.lastname: Francisco
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Luiz Felipe
authors.initials: LF
authors.lastname: Barella
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Sandra da Silva
authors.initials: SDS
authors.lastname: Silveira
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Lucas Paulo Jacinto
authors.initials: LPJ
authors.lastname: Saavedra
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Kelly Valério
authors.initials: KV
authors.lastname: Prates
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Vander Silva
authors.initials: VS
authors.lastname: Alves
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Claudinéia Conationi da Silva
authors.initials: CCDS
authors.lastname: Franco
authors.affiliation: Carlos Chagas Filho Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Rosiane Aparecida
authors.initials: RA
authors.lastname: Miranda
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Tatiane Aparecida
authors.initials: TA
authors.lastname: Ribeiro
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Laize Peron
authors.initials: LP
authors.lastname: Tófolo
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Ananda
authors.initials: A
authors.lastname: Malta
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: Vieira
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Kesia
authors.initials: K
authors.lastname: Palma-Rigo
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Audrei
authors.initials: A
authors.lastname: Pavanello
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Isabela Peixoto
authors.initials: IP
authors.lastname: Martins
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Veridiana Mota
authors.initials: VM
authors.lastname: Moreira
authors.affiliation: Institute of Health Sciences, Federal University of Mato Grosso, Sinop, MT, Brazil.
authors.forename: Júlio Cezar
authors.initials: JC
authors.lastname: de Oliveira
authors.affiliation: Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Paulo Cezar de Freitas
authors.initials: PCF
authors.lastname: Mathias
authors.affiliation: Department of Physiological Sciences (DCiF) - Biological Science Institute II (ICB-II), Room 220, Federal University of Goiás (UFG) - Campus II, Esperança Avenue s/n, CEP 74690-900, Goiânia, GO, Brazil. rodrigomellogomes@hotmail.com.
authors.forename: Rodrigo Mello
authors.initials: RM
authors.lastname: Gomes
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D050171:Dyslipidemias / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D005260:Female; D007328:Insulin / Q000032:analysis / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007774:Lactation / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008892:Milk / Q000737:chemistry; D009765:Obesity / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011765:Pyruvaldehyde / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D066007:Toxicokinetics; D015430:Weight Gain / Q000187:drug effects
chemical_list: D004785:Environmental Pollutants; D007328:Insulin; D011765:Pyruvaldehyde
keywords: AGEs; Diabetes; Dyslipidemia; Lactation; Metabolic programming; Methylglyoxal