A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight

Area of Science:

• Reproductive Biology
• Metabolic Syndrome
• Developmental Origins of Health and Disease

Background:

• Low birthweight (LBW) remains a persistent issue in Japan, with no decrease in incidence.
• Understanding the long-term health consequences of LBW is crucial for developing effective interventions.

Purpose of the Study:

• To establish a non-obese hyperglycemic mouse model born with LBW.
• To investigate the pathogenesis of hyperglycemia and insulin resistance in LBW offspring.

Main Methods:

• Transient intrauterine ischemia was induced in pregnant mice to create LBW offspring.
• Postnatal assessment included body composition, fasting blood glucose, serum insulin, and liver metabolite analysis.
• Insulin resistance was evaluated using the homeostasis model assessment (HOMA-IR).

Main Results:

• LBW pups exhibited significantly lower birthweight and remained underweight postnatally.
• Hyperglycemia, elevated serum insulin, and insulin resistance were observed in LBW offspring.
• Liver analysis revealed reduced ATP and NAD+ production, and increased lactic acid in LBW mice.

Conclusions:

• The developed mouse model mimics non-obese hyperglycemia in LBW offspring.
• Mitochondrial dysfunction and reduced lean body mass may contribute to myogenic insulin resistance in LBW individuals.
• This model provides a platform for studying LBW-related metabolic disorders.