Copyright
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Maternal low protein diet induces persistent expression changes in metabolic genes in male rats
Allan de Oliveira Lira, José Luiz de Brito Alves, Mariana Pinheiro Fernandes, Diogo Vasconcelos, David Filipe Santana, João Henrique da Costa-Silva, Béatrice Morio, Carol Góis Leandro, Luciano Pirola
Allan de Oliveira Lira, Diogo Vasconcelos, David Filipe Santana, Carol Góis Leandro, Department of Nutrition, Federal University of Pernambuco, Vitoria de Santo Antão, Pernambuco 55608680, Brazil
José Luiz de Brito Alves, Department of Nutrition, Federal University of Paraíba, Joao Pessoa 74556060, Brazil
Mariana Pinheiro Fernandes, Henrique da Costa-Silva, Luciano Pirola, Department of Physical Education and Sport Sciences, Federal University of Pernambuco, Vitoria de Santo Antão, Pernambuco 55608680, Brazil
Béatrice Morio, Luciano Pirola, Carmen (Cardiology, Metabolism and Nutrition) Laboratory, INSERM U1060, Lyon-1 University, South Lyon Medical Faculty, Pierre Benite 69310, France
Author contributions: de Oliveira Lira A performed experiments and data analysis and contributed to writing; de Brito Alves JL performed experiments and data analysis; Pinheiro Fernandes M performed experiments; Vasconcelos D performed experiments; Santana DF performed experiments; da Costa-Silva JH supervised the project and contributed to writing; Morio B contributed to writing; Leandro CG supervised the project, performed data analysis and contributed to writing; Pirola L supervised the project, wrote the final manuscript version and managed the submission process.
Supported by the CAPES/COFECUB, No. 797-14; the National Council for Research – Brazil, No. 477915/2012-4.
Institutional animal care and use committee statement: The experimental protocol was approved by the Ethical Committee of the Biological Sciences Centre (protocol 23076 062778/2014-38), Federal University of Pernambuco, Brazil.
Conflict-of-interest statement: The authors declare no competing financial interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Luciano Pirola, PhD, Senior Researcher, Carmen (Cardiology, Metabolism and Nutrition) Laboratory, INSERM U1060, Lyon-1 University, South Lyon Medical Faculty Sector 2, CENS ELI-2D building, 165 Chemin du grand Revoyet, Pierre Benite 69310, France. luciano.pirola@univ-lyon1.fr
Received: December 12, 2019
Peer-review started: December 12, 2019
First decision: January 6, 2020
Revised: March 16, 2020
Accepted: March 30, 2020
Article in press: March 30, 2020
Published online: May 15, 2020
Processing time: 144 Days and 20.7 Hours
ARTICLE HIGHLIGHTS
Research background
Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age, both in experimental models and humans. Numerous adaptive responses to maternal protein restriction have been reported in metabolic tissues. However, the expression of glucose/fatty acid metabolism-related genes in adipose tissue and liver needs to be described.
Research motivation
To evaluate the metabolic impact of perinatal malnutrition, we determined malnutrition-associated gene expression alterations in liver and adipose tissue.
Research objectives
In the present study, we evaluated the alterations in gene expression of glycolytic/Krebs cycle genes (pyruvate dehydrogenase kinase 4 and citrate synthase), adipogenic and lipolytic genes and leptin in the adipose tissue of offspring rats at 30 d and 90 d of age exposed to maternal isocaloric low protein (LP) diet throughout gestation and lactation. We also evaluated these genes in the livers of the same animals as well as the gene expression of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1, forkhead box protein O1 and hepatocyte nuclear factor 4 and of gluconeogenic genes.
Research methods
Research methods included animal husbandry, RNA extraction, reverse transcription and quantitative PCR and appropriate statistical analysis.
Research results
In the adipose tissue, we observed a transitory (i.e., at 30 d) downregulation of pyruvate dehydrogenase kinase 4, citrate synthase and carnitine palmitoylacyltransferase 1b gene expression. Such transcriptional changes did not persist in adult LP rats (90 d), but we observed a tendency towards a decreased gene expression of leptin (P = 0.052). The liver featured some gene expression alterations comparable to the adipose tissue, such as pyruvate dehydrogenase kinase 4 downregulation at 30 d, and displayed other tissue-specific changes, including citrate synthase and fatty acid synthase upregulation, but pyruvate kinase downregulation at 30 d in the LP group and carnitine palmitoylacyltransferase 1b downregulation at 90 d. These gene alterations, together with previously described changes in gene expression in skeletal muscle, may account for the metabolic adaptations in response to maternal LP diet and highlight the occurrence of persistent transcriptional defects in key metabolic genes that may contribute to the development of metabolic alterations during the adult life as a consequence of perinatal malnutrition.
Research conclusions
We conclude that perinatal malnutrition relays long-lasting transcriptional alterations in metabolically active organs, i.e., the liver and adipose tissue.
Research perspectives
Our observations lay the basis for possible future research directed to human studies.
