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Pregnancy and lactation after Roux-en-Y gastric bypass worsen nonalcoholic fatty liver disease in obese rats and lead to differential programming of hepatic de novo lipogenesis in offspring

Published online by Cambridge University Press:  17 May 2021

Iala Milene Bertasso ,
Carla Bruna Pietrobon ,
Rosane Aparecida Ribeiro ,
Gabriela Moreira Soares ,
Janaina Chaves de Oliveira ,
Ana Claudia Paiva Alegre-Maller ,
Antonio Carlos Boschero ,
Allan Cezar Faria Araújo ,
Ana Tereza Bittencourt Guimarães  and
Maria Lúcia Bonfleur Open the ORCID record for Maria Lúcia Bonfleur [Opens in a new window]
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Iala Milene Bertasso
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Carla Bruna Pietrobon
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Rosane Aparecida Ribeiro
Affiliation:
Departamento de Biologia Geral, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa (UEPG), Ponta Grossa, PR, Brazil
Gabriela Moreira Soares
Affiliation:
Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
Janaina Chaves de Oliveira
Affiliation:
Laboratório de Fisiopatologia, Divisão de Pesquisa Integrada em Produtos Bioativos e Biociências, Universidade Federal do Rio de Janeiro, Campus UFRJ-Macaé, Macaé, RJ, Brazil
Ana Claudia Paiva Alegre-Maller
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Antonio Carlos Boschero
Affiliation:
Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
Allan Cezar Faria Araújo
Affiliation:
Centro de Ciências Médicas e Farmacêuticas, UNIOESTE, Cascavel, PR, Brazil
Ana Tereza Bittencourt Guimarães
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Maria Lúcia Bonfleur*
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Sandra Lucinei Balbo
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
*
Address for correspondence: Maria Lúcia Bonfleur, Endocrine Physiology and Metabolism Laboratory, Cascavel, PR, Brazil, Zip code: 858119-110. Email: [email protected]
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Abstract

Maternal obesity increases the risk of nonalcoholic fatty liver disease (NAFLD) in offspring. The Roux-en-Y gastric bypass (RYBG) is effective for achieving weight loss and ameliorates NAFLD. To determine whether these benefits are maintained after pregnancy and/or lactation, and whether they modulate hepatic morphofunction in the next generation, we evaluated hepatic lipid metabolism in Western diet (WD)-obese female rats that underwent RYGB and in their F1 offspring at adulthood. Female Wistar rats consumed a WD from 21 to 130 days of age, before being submitted to RYGB (WD-RYGB-F0) or SHAM (WD-SHAM-F0) operations. After 5 weeks, these females were mated with control male breeders, and the male and female F1 offspring were identified as WD-RYGB-F1 and WD-SHAM-F1. WD-RYGB-F0 dams exhibited lower serum lipids levels, but severe hepatic steatosis and pathological features of advanced liver injury. The hepatic proteins involved in lipogenesis were reduced in WD-RYGB-F0, as were the genes related to β-oxidation and bile acids (BAs). Although the female and male WD-RYGB-F1 groups did not exhibit hepatic steatosis, the livers of female WD-RYGB-F1 demonstrated higher amounts of lipogenic genes and proteins, while male WD-RYGB-F1 presented a similar downregulation of lipogenic factors to that seen in WD-RYGB-F0 dams. In contrast, maternal and offspring groups of both sexes displayed reductions in the expressions of genes involved in BAs physiology and gluconeogenesis. As such, RYGB aggravates NAFLD after pregnancy and lactation and induces a gender-dependent differential expression of the hepatic lipogenesis pathway in offspring, indicating that female WD-RYGB-F1 may be an increased risk of developing NAFLD.

Keywords

Bariatric operationpregnancy and lactationmaternal programmingnon-alcoholic fatty liver diseaseobesity
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 2 , April 2022 , pp. 263 - 273
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Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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