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Puberty as a DOHaD programming window: high-fat diet induces long-term hepatic dysfunction in male rats

Published online by Cambridge University Press:  13 November 2023

Beatriz Gonçalves dos Santos
Affiliation:
Department of Physiological Sciences, Laboratory of Endocrine Physiology and Metabolism, Federal University of Goiás, Goiânia, GO, Brazil
Rosiane Aparecida Miranda
Affiliation:
Department of Physiological Sciences, Laboratory of Endocrine Physiology, Institute of Biology Roberto Alcantara Gomes, Rio de Janeiro State University, Rio de Janeiro, Brazil
Lucas Paulo Jacinto Saavedra
Affiliation:
Department of Biotechnology, Genetics and Cell Biology, Laboratory of Secretion Cell Biology, State University of Maringá, Maringá, Brazil
Flávio Andrade Francisco
Affiliation:
Department of Biotechnology, Genetics and Cell Biology, Laboratory of Secretion Cell Biology, State University of Maringá, Maringá, Brazil
Maiara Vanusa Guedes Ribeiro
Affiliation:
Department of Biotechnology, Genetics and Cell Biology, Laboratory of Secretion Cell Biology, State University of Maringá, Maringá, Brazil
Anna Rebeka Oliveira Ferreira
Affiliation:
Department of Biotechnology, Genetics and Cell Biology, Laboratory of Secretion Cell Biology, State University of Maringá, Maringá, Brazil
Marcos Divino Ferreira-Junior
Affiliation:
Department of Physiological Sciences, Laboratory of Endocrine Physiology and Metabolism, Federal University of Goiás, Goiânia, GO, Brazil
Keilah Valéria Naves Cavalcante
Affiliation:
Department of Physiological Sciences, Laboratory of Endocrine Physiology and Metabolism, Federal University of Goiás, Goiânia, GO, Brazil
Carlos Henrique Xavier
Affiliation:
Department of Physiological Sciences, Federal University of Goiás, Goiânia, GO, Brazil
Egberto Gaspar de Moura
Affiliation:
Department of Physiological Sciences, Laboratory of Endocrine Physiology, Institute of Biology Roberto Alcantara Gomes, Rio de Janeiro State University, Rio de Janeiro, Brazil
Patrícia Cristina Lisboa
Affiliation:
Department of Physiological Sciences, Laboratory of Endocrine Physiology, Institute of Biology Roberto Alcantara Gomes, Rio de Janeiro State University, Rio de Janeiro, Brazil
Ariel Penha Carvalho da Mota
Affiliation:
Department of Physiological Sciences, Laboratory of Endocrine Physiology and Metabolism, Federal University of Goiás, Goiânia, GO, Brazil
Gustavo Rodrigues Pedrino
Affiliation:
Department of Physiological Sciences, Federal University of Goiás, Goiânia, GO, Brazil
James Andrew Armitage
Affiliation:
School of Medicine and IMPACT Institute, Deakin University, Waurn Ponds, Australia
Paulo Cezar de Freitas Mathias
Affiliation:
Department of Biotechnology, Genetics and Cell Biology, Laboratory of Secretion Cell Biology, State University of Maringá, Maringá, Brazil
Kesia Palma-Rigo
Affiliation:
Department of Biotechnology, Genetics and Cell Biology, Laboratory of Secretion Cell Biology, State University of Maringá, Maringá, Brazil
Rodrigo Mello Gomes*
Affiliation:
Department of Physiological Sciences, Laboratory of Endocrine Physiology and Metabolism, Federal University of Goiás, Goiânia, GO, Brazil
*
Corresponding author: R. M. Gomes; Email: gomesrm@ufg.br

Abstract

The aim of this study was to evaluate whether high-fat (HF) diet intake during puberty can program obesity as well as generate glucose imbalance and hepatic metabolic dysfunctions in adult life. Male Wistar rats were randomly assigned into two groups: rats fed standard chow (NF) and rats fed a HF from postnatal 30-day-old (PND30) until PND60. Then, both groups were fed a standard chow from PND60 until PND120. Euthanasia and samples collections occurred at PND120. HF animals were overweight (+11%) and had increased adiposity, hyperphagia (+12%), hyperglycaemia (+13%), hyperinsulinemia (+69%), and hypertriglyceridemia (+34%). Plasma glucose levels during intravenous glucose tolerance test (ivGTT) and intraperitoneal insulin tolerance test (ipITT) were also higher in the HF group, whereas Kitt was significantly lower (–34%), suggesting reduced insulin sensitivity. In the same sense, HF animals present pancreatic islets hypertrophy and high β-cell mass. HF animals also had a significant increase in blood glucose levels during pyruvate tolerance test, indicating increased gluconeogenesis. Hepatic morphology analyses showed an increase in lipid inclusion in the HF group. Moreover, PEPCK and FAS protein expression were higher in the livers of the HF animals (+79% and + 37%, respectively). In conclusion, HF during puberty causes obese phenotype leading to glucose dyshomeostasis and nonalcoholic fatty liver disease, which can be related to the overexpression of proteins PEPCK and FAS.

Type
Original Article
Copyright
© The Author(s), 2023. Published by Cambridge University Press in association with The International Society for Developmental Origins of Health and Disease (DOHaD)

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