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Hepatic lipid metabolism in adult rats using early weaning models: sex-related differences

Published online by Cambridge University Press:  10 June 2020

Iala Milene Bertasso
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Carla Bruna Pietrobon
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Beatriz Souza da Silva
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Rosiane Aparecida Miranda
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Maria Lucia Bonfleur
Laboratory of Endocrine Physiology and Metabolism, Center of Biological and Health Sciences, Western Paraná State University, Cascavel, PR, Brazil
Sandra Lucinei Balbo
Laboratory of Endocrine Physiology and Metabolism, Center of Biological and Health Sciences, Western Paraná State University, Cascavel, PR, Brazil
Alex Christian Manhães
Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Elaine Oliveira
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Egberto Gaspar de Moura
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Patricia Cristina Lisboa*
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Address for correspondence: Patricia Cristina Lisboa, Departamento de Ciências Fisiológicas – 5° and ar, Instituto de Biologia – Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87 – Rio de Janeiro, RJ20551-031, Brazil. Emails:;


Non-pharmacological early weaning (NPEW) induces liver damage in male progeny at adulthood; however, pharmacological early weaning (PEW) does not cause this dysfunction. To elucidate this difference in liver dysfunction between these two models and determine the phenotype of female offspring, de novo lipogenesis, β-oxidation, very low-density lipoprotein (VLDL) export, and gluconeogenesis in both sexes were investigated in the adult Wistar rats that were weaned after a normal period of lactation (control group) or early weaned either by restriction of access to the dams’ teats (NPEW group) or by reduction of dams’ milk production with bromocriptine (PEW group). The offspring received standard diet from weaning to euthanasia (PN180). NPEW males had higher plasma triglycerides and TyG index, liver triglycerides, and cholesterol by de novo lipogenesis, which leads to intracellular lipids accumulation. As expected, hepatic morphology was preserved in PEW males, but they showed increased liver triglycerides. The only molecular difference between PEW and NPEW males was in acetyl-CoA carboxylase-1 (ACC-1) and stearoyl-CoA desaturase-1 (SCD-1), which were lower in PEW animals. Both early weaning (EW) females had no changes in liver cholesterol and triglyceride contents, and the hepatic cytoarchitecture was preserved. The expression of microsomal triglyceride transfer protein was increased in both the female EW groups, which could constitute a protective factor. The changes in hepatic lipid metabolism in EW offspring were less marked in females. EW impacted in the hepatic cytoarchitecture only in NPEW males, which showed higher ACC-1 and SCD-1 when compared to the PEW group. As these enzymes are lipogenic, it could explain a worsened liver function in NPEW males.

Original Article
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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