J Korean Diabetes Assoc.  2003 Apr;27(2):115-122.

Fetal Protein Deficiency Causes Long Term Changes in Mitochondrial DNA Content of Liver and Muscle in Female Sprague-Dawley Rats

• Kim SK
• Kim MS
• Kim YY
• Park DJ
• Park KS
• Lee KU
• Lee HK

Abstract

BACKGROUND: Epidemiological data suggest a strong association between low birth weight and the increased risk of metabolic syndrome, including type 2 diabetes, hypertension and cardiovascular disease, in adult life. However, the underlying mechanisms are largely unknown. In our previous study, the mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes was decreased in patients with type 2 diabetes and insulin resistance. To test the hypothesis that mitochondrial changes may serve as a link between fetal under nutrition and insulin resistance in later life, the effects of fetal protein malnutrition on the mitochondria of the liver and skeletal muscle, the main sites of insulin action in adulthood, were investigated.
METHODS
Eight-week old female rats were divided into 2 groups and fed on either a control diet (casein 180 g/kg diet) (n=5) or a low protein diet (casein 80 g/kg diet) (n=7) for 15 days prior to mating. They were mated with 10 week-old male Sprague Dawley rats that had been fed on the control diet. The female offspring, born to the mothers fed the low protein diet, were randomly divided into 2 groups 4 weeks after birth, and weaned on either the low protein (low protein group, n=48) or control diet (resuscitated group, n=48). As a control group, the offspring born to the mothers fed the control diet were weaned on the control diet (n=48). The animals in each group were again randomly divided into 4 groups, and sacrificed at 5, 10, 15 and 20 weeks of age, respectively (n=12 per group). The body weight, liver and muscle mtDNA content were measured at weeks 5, 10, 15 and 20.
RESULTS
The mtDNA contents of the liver and skeletal muscle were reduced in fetal malnourished adult rats, and were not restored to normal levels even when proper nutrition was supplied after weaning.
CONCLUSION
Our findings indicate that under nutrition in early life causes long lasting changes in the mitochondria DNA content of the liver and muscles, which may contribute to the development of insulin resistance in later life.

Keyword

Thrifty phenotype; Insulin resistance; Mitochondrial DNA content; Diabetes mellitus

MeSH Terms

Adult
Animals
Body Weight
Cardiovascular Diseases
Diabetes Mellitus
Diet
Diet, Protein-Restricted
DNA
DNA, Mitochondrial*
Female*
Humans
Hypertension
Infant, Low Birth Weight
Infant, Newborn
Insulin
Insulin Resistance
Leukocytes
Liver*
Male
Malnutrition
Mitochondria
Mothers
Muscle, Skeletal
Muscles
Parturition
Protein Deficiency*
Rats
Rats, Sprague-Dawley*
Weaning
DNA
DNA, Mitochondrial
Insulin