Abstract
Alterations in the early life environment, including maternal undernutrition (UN) during pregnancy, can lead to increased risk of metabolic and cardiovascular disorders in offspring. Leptin treatment of neonates born to UN rats reverses the programmed metabolic phenotype, but the possible benefits of this treatment on bone tissue have not been defined. We describe for the first time the effects of neonatal leptin treatment on bone in adult offspring following maternal UN. Offspring from either UN or ad libitum-fed (AD) rats were treated with either saline or leptin (2.5 µg/ g.d on postnatal days (D)3–13) and were fed either a chow or high fat (HF) diet from weaning until study completion at D170. Analysis of micro-tomographic data of the left femur showed highly significant effects of UN on cortical and trabecular bone tissue indices, contributing to inferior microstructure and bone strength, almost all of which were reversed by early leptin life treatment. The HF fat diet negatively affected trabecular bone tissue, but the effects of only trabecular separation and number were reversed by leptin treatment. The negative effects of maternal UN on skeletal health in adult offspring might be prevented or attenuated by various interventions including leptin. Establishment of a minimal efficacious leptin dose warrants further study.
Highlights
Developmental Programming refers to the process whereby a stimulus experienced at a particular developmental stage results in alteration in phenotype that is retained in later life
Phenotypic differences described previously[6] included maternal UN resulting in significantly reduced birth weights, catch-up growth and increased adiposity in later life of offspring. These effects were exacerbated in the presence of a post-weaning high fat (HF) diet, and reversed in offspring treated with leptin
Alterations in the early life environment can result in increased risk of various metabolic and cardiovascular disorders in later life, which are amplified in the setting of a postnatal obesogenic environment
Summary
Developmental Programming refers to the process whereby a stimulus experienced at a particular developmental stage results in alteration in phenotype (structure, function or behaviour) that is retained in later life. In a range of experimental models neonatal leptin treatment reversed the postnatal consequences associated with both leptin deficiency and maternal UN4–10 Complete reversal of this UN phenotype in later life, including normalization of obesity, blood pressure and insulin sensitivity has been demonstrated[6] following neonatal leptin treatment; the effects of leptin were specific to UN offspring with no significant effects of treatment observed in offspring of control pregnancies. In the present study we investigated the role of maternal UN, neonatal leptin treatment, a post-weaning high fat (HF) diet and the interactions therein, on bone morphology in adult female rat offspring We hypothesised that these factors would be associated with significant changes in relevant features of bone morphology in adult offspring at the age of 170 days
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