Maternal obesity accelerates rat offspring metabolic ageing in a sex-dependent manner.

KEY POINTS

Maternal obesity predisposes to metabolic dysfunction in male and female offspring Maternal high-fat diet consumption prior to and throughout pregnancy and lactation accelerates offspring metabolic ageing in a sex-dependent manner This study provides evidence for programming-ageing interactions ABSTRACT: Human epidemiological studies show that maternal obesity (MO) shortens offspring life and health span. Life course cellular mechanisms involved in this developmental programming-ageing interaction are poorly understood. In a well-established rat MO model, female Wistar rats ate chow (controls (C)) or high energy, obesogenic diet to induce MO from weaning through pregnancy and lactation. Females were bred at postnatal day (PND) 120. Offspring (F ) of mothers on control diet (CF ) and MO diet (MOF ) delivered spontaneously at terms. Both CF and MOF ate C diet from weaning throughout the study. Offspring were killed at PND 36, 110, 450 and 650. We determined body and liver weights, liver and serum metabolite concentrations, hormones and oxidative stress biomarkers. Male and female CF body weight, total fat, adiposity index, serum leptin, insulin, insulin resistance, and liver weight, fat, triglycerides, malondialdehyde, reactive oxygen species and nitrotyrosine all rose with differing ageing trajectories. Female CF triglycerides were unchanged with age. Age-related increases were greater in MOF than CF in both sexes for all variables except glucose in males and females and cholesterol in males. Cholesterol fell in CF females but not MOF . Serum corticosterone levels were higher in male and female MOF than CF and declined with age. DHEA serum levels were lower in male and female MOF than CF . Liver antioxidant enzymes decreased with age (CF and MOF ).

CONCLUSIONS

exposure to the developmental challenge of MO accelerates progeny ageing metabolic and endocrine profiles in a sex specific manner, providing evidence for programming-ageing interactions.