AUTHOR=Vargas Rodrigo , Martins Isabela Peixoto , Matiusso Camila Cristina Ianoni , Casagrande Raiana Aparecida , Zara Camila Benan , Huppes de Souza Anna Carolina , Horst William Pereira , Sieklicki Taina Cristine , Becker Tania Cristina Alexandrino , Lucredi Naiara Cristina , Comar Jurandir Fernando , Malta Ananda , Mathias Paulo Cezar de Freitas 

TITLE=Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring

JOURNAL=Frontiers in Nutrition

VOLUME=Volume 9 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1062116

DOI=10.3389/fnut.2022.1062116

ISSN=2296-861X

ABSTRACT=Protein restriction during lactation can induce metabolic dysfunctions and have a huge impact on the phenotype induced in the offspring later in life. Objective: We tested whether the effects of maternal low-protein diet (LP) can be transmitted to F2 generation and increase their vulnerability to dietary insult at adulthood.   Methods: Female Wistar rats (F0) were fed either a low-protein diet (LP; 4% protein) during the first two weeks of lactation or a normal-protein diet (NP; 23% protein). Their female offspring (F1 generation) were maintained on a standard diet throughout the experiment. At adulthood, female F1 offspring from both groups (i.e NP-F1 and LP-F1 group) were bred to proven males, outside the experiment, to produce F2 offspring. Male F2 offspring from both groups (i.e NP-F2 and LP-F2 group) received standard diet until 60 days old, when then they received either a normal fat (NF; 4,5% fat) or high fat diet (HF; 35% fat) by 30 days. Results: At 90 days old, LPNF-F2 offspring had increased in lipogenesis and fasting insulinemia compared to NPNF-F2, without alteration in insulin sensitivity. HF caused increased gluconeogenesis and displayed glucose intolerance in LPHF-F2 compared to LPNF-F2, besides damage in lipid metabolism as steatosis grade 3, higher body weight, fat pad stores and hepatic lipid content. Conclusion: We concluded that the F0 maternal protein-restriction diet during lactation could induce a transgenerational effect on glucose and liver metabolism in F2 generation, making liver’ offspring more vulnerable to nutritional injury later in life.