Fetal and early postnatal protein malnutrition cause long-term changes in rat liver and muscle mitochondria.
Epidemiologic data suggest a strong association between low birth weight and increased risk of metabolic syndrome in adult life. However, the underlying mechanisms are largely unknown. To test the hypothesis that mitochondrial changes may serve as a link between poor nutrition in early life and insulin resistance in later life, we investigated the effect of protein malnutrition during gestation and lactation on mitochondria of the liver and skeletal muscle. Female offspring of Sprague-Dawley rats fed a low protein diet (casein, 80 g/kg) were randomly divided into two groups and weaned onto either the low protein diet or a control diet (casein, 180 g/kg). As a control group, offspring of rats fed the control diet were weaned onto the control diet. The rats in each group were randomly divided into four groups that were killed at 5, 10, 15 and 20 wk of age. Both mitochondrial DNA content and the expression of mitochondrial DNA-encoded genes in liver and muscle were measured. Mitochondrial transcription factor A and antioxidant enzyme activities were also determined. The mitochondrial DNA content of the liver and skeletal muscle were reduced in fetal and early postnatal malnourished rats even when proper nutrition was supplied after weaning. These changes were accompanied by a decrease in mitochondrial DNA-encoded gene expression; however, they were not dependent on mitochondrial transcriptional factor A. Our findings indicate that poor nutrition in early life causes long-lasting changes in mitochondria that may contribute to the development of insulin resistance in later life.
Park
Kyong Soo
KS
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kim
Suk Kyeong
SK
Kim
Min Seon
MS
Cho
Eun Young
EY
Lee
Jong Ho
JH
Lee
Ki-Up
KU
Pak
Youngmi Kim
YK
Lee
Hong Kyu
HK
D000375:Aging; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001835:Body Weight; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000097:blood; D004268:DNA-Binding Proteins; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D007333:Insulin Resistance; D015227:Lipid Peroxidation; D008099:Liver / Q000196:embryology / Q000201:enzymology; D008297:Male; D008930:Mitochondria, Liver / Q000737:chemistry*; D008931:Mitochondria, Muscle / Q000737:chemistry*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000196:embryology / Q000201:enzymology / Q000648:ultrastructure; D009245:NADH Dehydrogenase / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D011488:Protein Deficiency / Q000150:complications* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C489030:Tfam protein, rat; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D013482:Superoxide Dismutase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV