Programming Effects of Prenatal Glucocorticoid Exposure with a Postnatal High-Fat Diet in Diabetes Mellitus

Area of Science:

• Endocrinology
• Metabolic disease research
• Developmental origins of health and disease

Background:

• Chronic diseases often originate from early-life exposures, including prenatal events known as fetal programming.
• Glucocorticoids are used to mature lungs of premature infants, but their long-term metabolic effects combined with diet are unclear.
• High-fat diets are linked to insulin resistance, but their interaction with prenatal steroid exposure requires investigation.

Purpose of the Study:

• To investigate the combined effects of prenatal glucocorticoid exposure and postnatal high-fat diet on metabolic health in rat offspring.
• To assess impacts on liver, pancreas, muscle, and adipose tissue function and gene expression.

Main Methods:

• Pregnant Sprague-Dawley rats received dexamethasone or vehicle during late gestation.
• Male offspring were fed normal or high-fat diets from weaning until postnatal day 120.
• Intraperitoneal glucose tolerance tests (IPGTT) and serum insulin levels were measured.
• Gene and protein expression of insulin receptors and related pathways were analyzed in key metabolic tissues.

Main Results:

• The dexamethasone plus high-fat diet (DHF) group showed higher glucose levels during IPGTT compared to the vehicle plus high-fat diet (VHF) group.
• Liver insulin receptor and AMPK mRNA and protein levels were reduced in the DHF group.
• Insulin receptor and IRS-1 mRNA expression decreased in epididymal adipose tissue in both VHF and DHF groups.
• Prenatal steroid exposure exacerbated diet-induced insulin resistance.

Conclusions:

• Prenatal glucocorticoid exposure initiates "programming" in the liver and adipose tissue.
• Combined prenatal steroid exposure and postnatal high-fat diet significantly worsens insulin resistance.
• Early-life interventions are crucial for mitigating risks of metabolic diseases later in life.