Changes of mitochondrial DNA content in the male offspring of protein-malnourished rats.
Nutritional deprivation of the fetus and infant is associated with susceptibility to the development of impaired glucose tolerance or type 2 diabetes in adult life. Quantitative changes in mitochondrial DNA (mtDNA) seem to be associated with type 2 diabetes, but the effect of protein malnutrition on mtDNA content is not known. This study investigated the effects of protein malnutrition in fetus and early life on mtDNA content and glucose-insulin metabolism in adult life. Male offspring of dams fed a low-protein (LP) diet (8% casein) during pregnancy and lactation were weaned onto either a control (18% casein) diet (recuperated group, R) or a LP diet, and they were compared with the control group (C). The mtDNA content in the liver was lower in the R and LP groups than in the C group at 5 weeks of age, but higher in the R and LP groups than in the C group at 15 weeks of age. The mtDNA content in skeletal muscle and pancreas was significantly lower in the R and LP groups than in the C group at 25 weeks of age. Fetal-malnourished rats showed decreased pancreatic beta-cell mass and reduced insulin secretory responses to glucose load, but no differences in glucose tolerance or insulin sensitivity. Our findings imply that protein malnutrition in utero causes changes in mtDNA content, impaired beta-cell development, and insulin secretion, which may contribute to the development of type 2 diabetes in later life.
Park
Hyeong Kyu
HK
Department of Internal Medicine, SoonChunHyang University College of Medicine, Seoul, Korea.
Jin
Cheng Ji
CJ
Cho
Young Min
YM
Park
Do Joon
DJ
Shin
Chan Soo
CS
Park
Kyong Soo
KS
Kim
Seong Yeon
SY
Cho
Bo Youn
BY
Lee
Hong Kyu
HK
D000818:Animals; D001835:Body Weight; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000502:physiology* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000254:growth & development; D008297:Male; D009748:Nutrition Disorders / Q000503:physiopathology*; D011247:Pregnancy; D011502:Protein-Energy Malnutrition / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D004272:DNA, Mitochondrial; D007328:Insulin; D005947:Glucose