TY - JOUR
T1 - Maternal low-protein diet reduces skeletal muscle protein synthesis and mass via Akt-mTOR pathway in adult rats
AU - de Vasconcelos, Diogo Antonio Alves
AU - Nachbar, Renato Tadeu
AU - Pinheiro, Carlos Hermano
AU - do Amaral, Cátia Lira
AU - Crisma, Amanda Rabello
AU - Vitzel, Kaio Fernando
AU - Abreu, Phablo
AU - Alonso-Vale, Maria Isabel
AU - Lopes, Andressa Bolsoni
AU - Bento-Santos, Adriano
AU - Falcão-Tebas, Filippe
AU - de Santana, David Filipe
AU - do Nascimento, Elizabeth
AU - Curi, Rui
AU - Pithon-Curi, Tania Cristina
AU - Hirabara, Sandro Massao
AU - Leandro, Carol Góis
N1 - Funding Information:
This research was carried out with financial support from the Coordination for the Improvement of Higher Level/Education Personnel (CAPES), the Pernambuco State Research and Technology Foundation (FACEPE) (protocol no. PNPD Facepe/Capes APQ-0800-2.07/16), the National Council for Scientific and Technological Development (CNPq, protocol no. 141891/2012-2), and the São Paulo State Research Foundation (FAPESP). DAAV received a fellowship grant (FACEPE, protocol no. BCT-0205-4.05/18).
Publisher Copyright:
Copyright © 2022 de Vasconcelos, Nachbar, Pinheiro, do Amaral, Crisma, Vitzel, Abreu, Alonso-Vale, Lopes, Bento-Santos, Falcão-Tebas, de Santana, do Nascimento, Curi, Pithon-Curi, Hirabara and Leandro.
PY - 2022/8/30
Y1 - 2022/8/30
N2 - 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.
AB - 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.
KW - Akt expression
KW - developmental plasticity
KW - insulin resistance
KW - low-protein diet
KW - protein metabolism
UR - http://www.scopus.com/inward/record.url?scp=85138270289&partnerID=8YFLogxK
U2 - 10.3389/fnut.2022.947458
DO - 10.3389/fnut.2022.947458
M3 - Article
C2 - 36110404
AN - SCOPUS:85138270289
SN - 2296-861X
VL - 9
JO - Frontiers in Nutrition
JF - Frontiers in Nutrition
M1 - 947458
ER -