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

Abstract

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 (F₁ ) of mothers on control diet (CF₁ ) and MO diet (MOF₁ ) delivered spontaneously at terms. Both CF₁ and MOF₁ 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 CF₁ 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 CF₁ triglycerides were unchanged with age. Age-related increases were greater in MOF₁ than CF₁ in both sexes for all variables except glucose in males and females and cholesterol in males. Cholesterol fell in CF₁ females but not MOF₁ . Serum corticosterone levels were higher in male and female MOF₁ than CF₁ and declined with age. DHEA serum levels were lower in male and female MOF₁ than CF₁ . Liver antioxidant enzymes decreased with age (CF₁ and MOF₁ ).

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.

Keywords: ageing; developmental programming; liver fat; maternal obesity; metabolism; oxidative stress.