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10.3390/nu13103417
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Article

Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet

by
Jiaqi Cui
1,†,
Lin Song
2,3,†,
Rui Wang
2,
Shuyuan Hu
2,
Zhao Yang
4,
Zengtie Zhang
5,
Bo Sun
2,3,* and
Wei Cui
1,*
1
Department of Endocrinology and Second Department of Geriatrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
2
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
3
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi’an Jiaotong University, Xi’an 710061, China
4
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
5
Department of Pathology, Xi’an Jiao Tong University Health Science Center, Xi’an 710061, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Nutrients 2021, 13(10), 3417; https://doi.org/10.3390/nu13103417
Submission received: 25 August 2021 / Revised: 25 September 2021 / Accepted: 26 September 2021 / Published: 28 September 2021
(This article belongs to the Section Nutrition in Women)
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Abstract

Maternal high-fat (HF) diet is associated with offspring metabolic disorder. This study intended to determine whether maternal metformin (MT) administration during gestation and lactation prevents the effect of maternal HF diet on offspring’s skeletal muscle (SM) development and metabolism. Pregnant Sprague-Dawley rats were divided into four groups according to maternal diet {CHOW (11.8% fat) or HF (60% fat)} and MT administration {control (CT) or MT (300 mg/kg/day)} during gestation and lactation: CH-CT, CH-MT, HF-CT, HF-MT. All offspring were weaned on CHOW diet. SM was collected at weaning and 18 weeks in offspring. Maternal metformin reduced plasma insulin, leptin, triglyceride and cholesterol levels in male and female offspring. Maternal metformin increased MyoD expression but decreased Ppargc1a, Drp1 and Mfn2 expression in SM of adult male and female offspring. Decreased MRF4 expression in SM, muscle dysfunction and mitochondrial vacuolization were observed in weaned HF-CT males, while maternal metformin normalized them. Maternal metformin increased AMPK phosphorylation and decreased 4E-BP1 phosphorylation in SM of male and female offspring. Our data demonstrate that maternal metformin during gestation and lactation can potentially overcome the negative effects of perinatal exposure to HF diet in offspring, by altering their myogenesis, mitochondrial biogenesis and dynamics through AMPK/mTOR pathways in SM.
Keywords: maternal diet; metformin; skeletal muscle; mitochondria; AMPK; mTOR maternal diet; metformin; skeletal muscle; mitochondria; AMPK; mTOR
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MDPI and ACS Style

Cui, J.; Song, L.; Wang, R.; Hu, S.; Yang, Z.; Zhang, Z.; Sun, B.; Cui, W. Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet. Nutrients 2021, 13, 3417. https://doi.org/10.3390/nu13103417

AMA Style

Cui J, Song L, Wang R, Hu S, Yang Z, Zhang Z, Sun B, Cui W. Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet. Nutrients. 2021; 13(10):3417. https://doi.org/10.3390/nu13103417

Chicago/Turabian Style

Cui, Jiaqi, Lin Song, Rui Wang, Shuyuan Hu, Zhao Yang, Zengtie Zhang, Bo Sun, and Wei Cui. 2021. "Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet" Nutrients 13, no. 10: 3417. https://doi.org/10.3390/nu13103417

APA Style

Cui, J., Song, L., Wang, R., Hu, S., Yang, Z., Zhang, Z., Sun, B., & Cui, W. (2021). Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet. Nutrients, 13(10), 3417. https://doi.org/10.3390/nu13103417

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