Maternal low-protein diet reduces skeletal muscle protein synthesis and mass via Akt-mTOR pathway in adult rats

Diogo Antonio Alves de Vasconcelos, Renato Tadeu Nachbar, Carlos Hermano Pinheiro, Cátia Lira do Amaral, Amanda Rabello Crisma, Kaio Fernando Vitzel, Phablo Abreu, Maria Isabel Alonso-Vale, Andressa Bolsoni Lopes, Adriano Bento-Santos, Filippe Falcão-Tebas, David Filipe de Santana, Elizabeth do Nascimento, Rui Curi, Tania Cristina Pithon-Curi, Sandro Massao Hirabara, Carol Góis Leandro

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Several studies have demonstrated that a maternal low-protein diet induces long-term metabolic disorders, but the involved mechanisms are unclear. This study investigated the molecular effects of a low-protein diet during pregnancy and lactation on glucose and protein metabolism in soleus muscle isolated from adult male rats. Female rats were fed either a normal protein diet or low-protein diet during gestation and lactation. After weaning, all pups were fed a normal protein diet until the 210th day postpartum. In the 7th month of life, mass, contractile function, protein and glucose metabolism, and the Akt-mTOR pathway were measured in the soleus muscles of male pups. Dry weight and contractile function of soleus muscle in the low-protein diet group rats were found to be lower compared to the control group. Lipid synthesis was evaluated by measuring palmitate incorporation in white adipose tissue. Palmitate incorporation was higher in the white adipose tissue of the low-protein diet group. When incubated soleus muscles were stimulated with insulin, protein synthesis, total amino acid incorporation and free amino acid content, glucose incorporation and uptake, and glycogen synthesis were found to be reduced in low-protein diet group rats. Fasting glycemia was higher in the low-protein diet group. These metabolic changes were associated with a decrease in Akt and GSK-3β signaling responses to insulin and a reduction in RPS6 in the absence of the hormone. There was also notably lower expression of Akt in the isolated soleus muscle of low-protein diet group rats. This study is the first to demonstrate how maternal diet restriction can reduce skeletal muscle protein and mass by downregulating the Akt-mTOR pathway in adulthood.

Original languageEnglish
Article number947458
Number of pages12
JournalFrontiers in Nutrition
Publication statusPublished - 30 Aug 2022


  • Akt expression
  • developmental plasticity
  • insulin resistance
  • low-protein diet
  • protein metabolism

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