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

IntroductionProtein restriction during lactation can induce metabolic dysfunctions and has a huge impact on the offspring’s phenotype later in its life. We tested whether the effects of a maternal low-protein diet (LP) in rats can be transmitted to the F2 generation and increase their vulnerability...

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Main Authors: Rodrigo Vargas, Isabela Peixoto Martins, Camila Cristina Ianoni Matiusso, Raiana Aparecida Casagrande, Camila Benan Zara, Anna Carolina Huppes de Souza, William Pereira Horst, Taina Cristine Sieklicki, Tania Cristina Alexandrino Becker, Naiara Cristina Lucredi, Jurandir Fernando Comar, Ananda Malta, Paulo Cezar de Freitas Mathias
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Nutrition
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Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2022.1062116/full
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author Rodrigo Vargas
Rodrigo Vargas
Isabela Peixoto Martins
Isabela Peixoto Martins
Isabela Peixoto Martins
Camila Cristina Ianoni Matiusso
Camila Cristina Ianoni Matiusso
Raiana Aparecida Casagrande
Camila Benan Zara
Anna Carolina Huppes de Souza
William Pereira Horst
Taina Cristine Sieklicki
Tania Cristina Alexandrino Becker
Naiara Cristina Lucredi
Jurandir Fernando Comar
Ananda Malta
Paulo Cezar de Freitas Mathias
author_facet Rodrigo Vargas
Rodrigo Vargas
Isabela Peixoto Martins
Isabela Peixoto Martins
Isabela Peixoto Martins
Camila Cristina Ianoni Matiusso
Camila Cristina Ianoni Matiusso
Raiana Aparecida Casagrande
Camila Benan Zara
Anna Carolina Huppes de Souza
William Pereira Horst
Taina Cristine Sieklicki
Tania Cristina Alexandrino Becker
Naiara Cristina Lucredi
Jurandir Fernando Comar
Ananda Malta
Paulo Cezar de Freitas Mathias
author_sort Rodrigo Vargas
collection DOAJ
description IntroductionProtein restriction during lactation can induce metabolic dysfunctions and has a huge impact on the offspring’s phenotype later in its life. We tested whether the effects of a maternal low-protein diet (LP) in rats can be transmitted to the F2 generation and increase their vulnerability to dietary insults in adulthood.MethodsFemale Wistar rats (F0) were fed either a low-protein diet (LP; 4% protein) during the first 2 weeks of lactation or a normal-protein diet (NP; 23% protein). The female offspring (F1 generation) were maintained on a standard diet throughout the experiment. Once adulthood was reached, female F1 offspring from both groups (i.e., NP-F1 and LP-F1) were bred to proven males, outside the experiment, to produce the F2 generation. Male F2 offspring from both groups (NP-F2 and LP-F2 groups) received a standard diet until 60 days old, at which point they received either a normal fat (NF; 4.5% fat) or a high fat diet (HF; 35% fat) for 30 days.ResultsAt 90 days old, LPNF-F2 offspring had increased lipogenesis and fasting insulinemia compared to NPNF-F2, without alteration in insulin sensitivity. HF diet caused increased gluconeogenesis and displayed glucose intolerance in LPHF-F2 offspring compared to LPNF-F2 offspring. Additionally, the HF diet led to damage to lipid metabolism (such as steatosis grade 3), higher body weight, fat pad stores, and hepatic lipid content.DiscussionWe concluded that an F0 maternal protein restricted diet during lactation can induce a transgenerational effect on glucose and liver metabolism in the F2 generation, making the offspring’s liver more vulnerable to nutritional injury later in life.
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spelling doaj.art-fd56a51bd7044b39acf3e8a8b3eb9afb2023-01-10T21:43:33ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2023-01-01910.3389/fnut.2022.10621161062116Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspringRodrigo Vargas0Rodrigo Vargas1Isabela Peixoto Martins2Isabela Peixoto Martins3Isabela Peixoto Martins4Camila Cristina Ianoni Matiusso5Camila Cristina Ianoni Matiusso6Raiana Aparecida Casagrande7Camila Benan Zara8Anna Carolina Huppes de Souza9William Pereira Horst10Taina Cristine Sieklicki11Tania Cristina Alexandrino Becker12Naiara Cristina Lucredi13Jurandir Fernando Comar14Ananda Malta15Paulo Cezar de Freitas Mathias16Department of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, BrazilHealth Sciences Center, UniCesumar, Maringá, BrazilDepartment of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, BrazilHealth Sciences Center, UniCesumar, Maringá, BrazilDepartment of Morphological Sciences, State University of Maringá, Maringá, BrazilDepartment of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, BrazilHealth Sciences Center, UniCesumar, Maringá, BrazilHealth Sciences Center, UniCesumar, Maringá, BrazilDepartment of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, BrazilDepartment of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, BrazilHealth Sciences Center, UniCesumar, Maringá, BrazilHealth Sciences Center, UniCesumar, Maringá, BrazilDepartment of Basic Health Sciences, State University of Maringá, Maringá, BrazilDepartment of Biochemistry, State University of Maringá, Maringá, BrazilDepartment of Biochemistry, State University of Maringá, Maringá, BrazilDepartment of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, BrazilDepartment of Biotechnology, Genetics, and Cellular Biology, State University of Maringá, Maringá, BrazilIntroductionProtein restriction during lactation can induce metabolic dysfunctions and has a huge impact on the offspring’s phenotype later in its life. We tested whether the effects of a maternal low-protein diet (LP) in rats can be transmitted to the F2 generation and increase their vulnerability to dietary insults in adulthood.MethodsFemale Wistar rats (F0) were fed either a low-protein diet (LP; 4% protein) during the first 2 weeks of lactation or a normal-protein diet (NP; 23% protein). The female offspring (F1 generation) were maintained on a standard diet throughout the experiment. Once adulthood was reached, female F1 offspring from both groups (i.e., NP-F1 and LP-F1) were bred to proven males, outside the experiment, to produce the F2 generation. Male F2 offspring from both groups (NP-F2 and LP-F2 groups) received a standard diet until 60 days old, at which point they received either a normal fat (NF; 4.5% fat) or a high fat diet (HF; 35% fat) for 30 days.ResultsAt 90 days old, LPNF-F2 offspring had increased lipogenesis and fasting insulinemia compared to NPNF-F2, without alteration in insulin sensitivity. HF diet caused increased gluconeogenesis and displayed glucose intolerance in LPHF-F2 offspring compared to LPNF-F2 offspring. Additionally, the HF diet led to damage to lipid metabolism (such as steatosis grade 3), higher body weight, fat pad stores, and hepatic lipid content.DiscussionWe concluded that an F0 maternal protein restricted diet during lactation can induce a transgenerational effect on glucose and liver metabolism in the F2 generation, making the offspring’s liver more vulnerable to nutritional injury later in life.https://www.frontiersin.org/articles/10.3389/fnut.2022.1062116/fullmetabolic programmingmaternal malnutritionsteatosisthrifty phenotype hypothesismetabolism
spellingShingle Rodrigo Vargas
Rodrigo Vargas
Isabela Peixoto Martins
Isabela Peixoto Martins
Isabela Peixoto Martins
Camila Cristina Ianoni Matiusso
Camila Cristina Ianoni Matiusso
Raiana Aparecida Casagrande
Camila Benan Zara
Anna Carolina Huppes de Souza
William Pereira Horst
Taina Cristine Sieklicki
Tania Cristina Alexandrino Becker
Naiara Cristina Lucredi
Jurandir Fernando Comar
Ananda Malta
Paulo Cezar de Freitas Mathias
Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring
Frontiers in Nutrition
metabolic programming
maternal malnutrition
steatosis
thrifty phenotype hypothesis
metabolism
title Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring
title_full Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring
title_fullStr Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring
title_full_unstemmed Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring
title_short Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring
title_sort protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring
topic metabolic programming
maternal malnutrition
steatosis
thrifty phenotype hypothesis
metabolism
url https://www.frontiersin.org/articles/10.3389/fnut.2022.1062116/full
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