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The absence of lactation after pregnancy induces long-term lipid accumulation in maternal liver of mice

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Vicente, Julia Modesto [1] ; Teixeira, Caio Jordao [1] ; Santos-Silva, Junia Carolina [1] ; de Souza, Dailson Nogueira [1] ; Tobar, Natalia [2] ; Furtuoso, Fabiola Sales [1] ; Adabo, Isabel Gouveia [1] ; Sodre, Frhancielly Shirley [3] ; Murata, Gilson [3] ; Bordin, Silvana [3] ; Anhe, Gabriel Forato [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Dept Pharmacol, Fac Med Sci, 105 Alexander Fleming St, BR-13084971 Campinas, SP - Brazil
[2] Univ Estadual Campinas, Dept Radiol, Fac Med Sci, BR-13084971 Campinas, SP - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Life Sciences; v. 217, p. 261-270, JAN 15 2019.
Citações Web of Science: 0

Aims: The present investigation evaluated whether pregnancy followed by lactation exerts long-term impacts on maternal hepatic lipid metabolism. Main methods: Female mice were subjected to two pregnancies, after which they were either allowed to breastfeed their pups for 21 days (L21) or had their litter removed (L0). Age-matched virgin mice were used as controls (CTL). Three months after the second delivery, serum was collected for lipid profiling, and fragments of liver were used to assess lipid content and to evaluate the key steps of de novo non-esterified fatty acid (NEFA) synthesis, esterification and beta-oxidation, very low density lipoprotein (VLDL) assembly and secretion and autophagy. Key findings: L0 exhibited a significant increase in hepatic TG and reduced apolipoprotein B-100 (ApoB-100) expression. L21 mice had increased ATP citrate lyase (ACLY) activity and reduced acetyl-CoA carboxylase (ACC) phosphorylation but no increased hepatic TG. On the other hand, L21 mice had reduced hepatic sequestosome 1 (SQSTM1/p62) levels. Increased high density lipoprotein (HDL) cholesterol and hepatic apolipoprotein A-1 (ApoA-1) expression were found exclusively in L21. Significance: The present study reveals that long-term hepatic lipid accumulation is induced by the history of pregnancy without lactation. On the other hand, reduced SQSTM1/p62 levels indicate that increased autophagic flux during life may prevent hepatic fat in dams subjected to lactation. Lactation after pregnancy is also obligatory for a long-term increase in maternal HDL. The present data may contribute to the understanding of the mechanisms leading to elevated cardiometabolic risk in women limited to short periods of lactation. (AU)

Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
Beneficiário:Licio Augusto Velloso
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 15/12680-1 - Estudo dos impactos em longo prazo da duração da lactação no metabolismo energético materno: participação de microRNAs hepáticos
Beneficiário:Gabriel Forato Anhê
Linha de fomento: Auxílio à Pesquisa - Regular