Prenatal low-protein and postnatal high-fat diets induce rapid adipose tissue growth by inducing Igf2 expression in...

Area of Science:

• Nutritional Epigenetics
• Developmental Origins of Health and Disease
• Metabolic Syndrome

Background:

• Maternal low-protein (LP) diets lead to low birth weight and accelerated catch-up growth, increasing later-life obesity and glucose intolerance.
• The impact of postnatal high-fat (HF) diets on offspring obesity and insulin resistance, particularly concerning adipose tissue metabolism and DNA methylation, remains unclear.

Purpose of the Study:

• To investigate the combined effects of prenatal LP and postnatal HF diets on offspring adipose tissue growth, insulin-like growth factor 2 (Igf2) expression, and DNA methylation.
• To determine if these dietary interventions influence adipocyte size and insulin sensitivity, contributing to metabolic dysfunction.

Main Methods:

• Obese-prone Sprague-Dawley rats were fed either LP (8% protein) or normal protein diets throughout gestation and lactation.
• Offspring were weaned onto either normal fat (10%) or HF (45%) diets for 12 weeks.
• Measurements included adipose tissue growth rate, Igf2 mRNA expression, DNA methylation, adipocyte size, and insulin sensitivity.

Main Results:

• The combination of prenatal LP and postnatal HF diets significantly increased adipose tissue growth rate (up to 26-fold).
• These diets also elevated adipose tissue Igf2 mRNA levels and DNA methylation, increased the proportion of small adipocytes, and reduced insulin sensitivity.
• This dietary pattern promoted adipose tissue catch-up growth and impaired metabolic health.

Conclusions:

• Prenatal LP and postnatal HF diets induce adipose tissue catch-up growth via altered Igf2 gene expression and DNA methylation in adipocytes.
• These epigenetic and metabolic changes increase the risk of obesity and type 2 diabetes in offspring.
• Early life nutrition significantly impacts long-term metabolic health and disease susceptibility.