Prenatal Low-Protein Diet Affects Mitochondrial Structure and Function in the Skeletal Muscle of Adult Female Offspring

被引:4
作者
Vidyadharan, Vipin A. [1 ]
Betancourt, Ancizar [1 ]
Smith, Craig [2 ]
Yallampalli, Chandrasekhar [1 ]
Blesson, Chellakkan S. [3 ,4 ]
机构
[1] Baylor Coll Med, Dept Obstet & Gynecol, Basic Sci Perinatol Res Labs, Houston, TX 77030 USA
[2] Agilent Technol, Santa Clara, CA 95051 USA
[3] Baylor Coll Med, Dept Obstet & Gynecol, Reprod Endocrinol & Infertil Div, Houston, TX 77030 USA
[4] Texas Childrens Hosp, Family Fertil Ctr, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
developmental programming; glucose intolerance; insulin resistance; mitochondria; low-protein diet; DEPENDENT DIABETES-MELLITUS; ELECTRON-TRANSPORT CHAIN; INSULIN-RESISTANCE; OXIDATIVE-PHOSPHORYLATION; MITOFUSIN; OVERNUTRITION PROGRAMS; GASTROCNEMIUS-MUSCLES; GLUCOSE-TRANSPORT; DNA METHYLATION; COMPLEX-I;
D O I
10.3390/nu14061158
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Gestational low-protein (LP) diet leads to glucose intolerance and insulin resistance in adult offspring. We had earlier demonstrated that LP programming affects glucose disposal in females. Mitochondrial health is crucial for normal glucose metabolism in skeletal muscle. In this study, we sought to analyze mitochondrial structure, function, and associated genes in skeletal muscles to explore the molecular mechanism of insulin resistance LP-programmed female offspring. On day four of pregnancy, rats were assigned to a control diet containing 20% protein or an isocaloric 6% protein-containing diet. Standard laboratory diet was given to the dams after delivery until the end of weaning and to pups after weaning. Gestational LP diet led to changes in mitochondrial ultrastructure in the gastrocnemius muscles, including a nine-fold increase in the presence of giant mitochondria along with unevenly formed cristae. Further, functional analysis showed that LP programming caused impaired mitochondrial functions. Although the mitochondrial copy number did not show significant changes, key genes involved in mitochondrial structure and function such as Fis1, Opa1, Mfn2, Nrf1, Nrf2, Pgc1b, Cox4b, Esrra, and Vdac were dysregulated. Our study shows that prenatal LP programming induced disruption in mitochondrial ultrastructure and function in the skeletal muscle of female offspring.
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页数:16
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